Literature DB >> 33665257

Data on the in vitro and in vivo anti-tumor effects of itraconazole, paclitaxel, and the two in combination in HT-29 and YM-1 cancer cell line and HT-29 colon cancer xenograft models.

Mahdi Ghadi1, Seyed Jalal Hosseinimehr1, Fereshteh Talebpour Amiri2, Alireza Mardanshahi3, Zohreh Noaparast1.   

Abstract

Colon cancer is one of the fatal cancers in the world that metastatic potential and resistance to chemotherapy drugs are outstanding causes of cancer-induced mortality [1], [2], [3], [4]. We have investigated in vitro and in vivo anti-cancer effect of itraconazole and paclitaxel alone and their anti-cancer synergistic effect through MTT assay in YM-1 and HT-29 cell lines and in HT-29 tumor-bearing nude mice. Histopathological experiment was done for further assessment. Also, we evaluated the inhibitory effect of itraconazole on P-gp using specific in vivo biodistribution through 99mTc-MIBI uptake. 99mTc-MIBI, a myocardial perfusion imaging agent, is a useful radiotracer in diagnosis of some tumors and the liver and tumor accumulation of 99mTc-MIBI is changed by P-gp regulators [5], [6], [7], [8]. The data presented in this article are related to the research paper entitled "Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice". We hope our preliminary data to be helpful to design the chemotherapy regimen schedule with Itraconazole and Paclitaxel.
© 2021 The Authors.

Entities:  

Keywords:  99mTc-MIBI; Itraconazole (ITCZ); P-gp regulator; Paclitaxel (PTX)

Year:  2021        PMID: 33665257      PMCID: PMC7903292          DOI: 10.1016/j.dib.2021.106862

Source DB:  PubMed          Journal:  Data Brief        ISSN: 2352-3409


Specifications Table

Value of the Data

The presented data provided experimental evidence for the potential anticancer effect of Itraconazole and Paclitaxel and the two in combination in human colon cancer in both in vitro and in vivo xenograft model. The data provided valuable information of anti-tumor efficacy of Itraconazole, a commercially cheap and available antifungal drug, and paclitaxel, a commonly used drug for the treatment of ovarian, breast, head and neck and lung cancer, and their Synergistic anti-tumor effects in nude mice xenograft model of HT-29 cells. These data may give additional insight to oncologist to design new chemotherapy regimen with Itraconazole and Paclitaxel in colon cancer. The data provided valuable evidence for researchers to investigate the anti-cancer effect of Itraconazole and Paclitaxel and the two in combination using another similar cellular model.

Data Description

Recently we have reported that in vitro and in vivo anti-cancer effect of itraconazole, paclitaxel and the two in combination in YM-1 and HT-29 cell lines and HT-29 bearing nude mice [9]. Here, we present raw data regarding the anti-cancer effect of these drugs. Detail raw and analysis data on Cytotoxic effects summarizes in Table 1. Table 2 demonstrates the changes in tumor volume measurements during treatment period in itraconazole, paclitaxel and itraconazole+ paclitaxel-treated nude mice. Notable, the animal experiment was performed by following two treatment protocol: 1) itraconazole (20 mg/Kg), paclitaxel (20 mg/Kg), itraconazole (20 mg/Kg) + paclitaxel (20 mg/Kg). 2) itraconazole (10 mg/Kg), paclitaxel (20 mg/Kg), itraconazole (10 mg/Kg) + paclitaxel (20 mg/Kg). Itraconazole-induced liver toxicity at dose of 20 mg/Kg caused to lessen the dose of itraconazole to 10 mg/Kg. Fig. 1 shows the itraconazole-induced hepatotoxicity at dose of 20 mg/Kg. 99mTc-MIBI biodistribution raw data are presents in Table 3.
Table 1

The in vitro cell cytotoxicity of itraconazole alone, paclitaxel alone and itraconazole+ paclitaxel co-treatment in YM-1 and HT-29 cell lines.

Cell survival %= (absorption of treated / absorbed Control Cells) × 100%.
Cell48 h
72 h
ControlITCZPTXITCZ+PTXControlITCZPTXITCZ+PTX
HT-29107.413111.8305100.205716.9721977.7154595.665476812.238653759.790922998
95.3232683.9309783.6984716.73969121.264763.8449770518.3579806217.84803672
92.7658174.8636362.5413616.507299.6430489.7501274947.0168281537.53187149
83.9309795.5557557.6589554.40401105.7624145.334013331.6165221812.95257522
89.7433685.3259462.0763777.1885971.4941483.7327893943.2432432413.36053034
94.6257773.23616100.670753.93901102.8047108.516063270.4742478311.72870984
135.545157.399662.7738546.0341694.4416183.2228454949.2605813421.7236104
129.500195.0907653.7065222.55209133.503382.1009688977.5114737411.21876594
79.7460484.3959623.0170845.1041899.4390695.2575216712.2386537513.87047425
131.127688.3483961.6113741.3842497.09332100.662927111.3207547211.4227435
109.27392.5333165.0988137.19932123.814473.0239673646.3029066823.55940847
71.8411948.35912109.505530.6894472.6160178.0214176448.2406935214.07445181
110.900599.7406846.7316529.2944683.12086127.485976544.4671086210.50484447
70.67871136.707530.6894428.8294797.2973107.598164211.2187659417.84803672
76.491175.0961324.4120525.8070383.01887130.953595150.2804691513.76848547
56.0314873.4686648.8241125.57453124.4263111.779704245.5889852117.13411525
108.808110.900528.8294724.64455117.0831120.44875069.8929117810.3008669
122.060394.8582734.1768823.4820797.3992990.1580826111.2187659412.13666497
47.6616396.0207529.7594622.3195995.25752114.737378937.7358490610.60683325
73.70115110.2033.71993222.087189.4441676.2876083611.3207547210.50484447
119.967828.8294722.3195921.15711122.386566.1907190246.3029066812.44263131
139.9624114.620438.8267920.9246299.8470276.1856195848.2406935212.13666497
135.0888.3483922.5520920.6921297.2973120.856705818.3579806214.07445181
117.1779152.517279.0485620.6921293.8296880.0611932746.3029066812.13666497
95.78825142.752461.8438719.7621477.7154595.665476812.238653759.790922998
104.8556113.922939.0592918.13467121.264763.8449770518.3579806217.84803672
Mean10097.263752.0522230.0813710096.7448580735.3646098914.69488356
SD25.2472329.2154527.0722814.7738716.7305922.0196777619.933801936.021501633

YM-1104.632977.2630160.1568175.2672879.1519438.3195938.005532.35179
89.2373574.4119765.8588762.4376387.0043237.3773131.723631.7236
103.492577.2630173.2715670.4205399.2540238.6336938.9477832.03769
86.9565289.8075673.2715666.9992991.4016534.5504539.5759735.17864
74.6970886.3863285.245968.9950197.6835533.9222634.8645537.37731
110.620188.3820472.9864662.4376373.8123338.005540.2041637.6914
91.8032896.0798368.139768.70991112.760135.8068337.0632132.66588
88.0969490.9479753.8845351.88881121.554839.8900735.4927431.7236
98.6457699.7861772.7013565.8588784.4915632.6658837.0632133.92226
100.926678.4034272.7013557.87598120.298431.409535.8068333.29407
82.9650783.2501882.6799782.1097692.3439332.3517935.8068332.35179
88.0969482.9650769.5652259.301583.2351832.9799837.3773131.7236
101.781984.1054975.5523958.7312983.2351834.8645539.8900732.03769
103.777693.228882.6799759.0163978.2096632.3517935.8068333.60817
77.2630178.6885284.3905951.0335116.215232.9799836.1209334.55045
110.620188.0969467.2843951.60371116.215233.2940740.2041633.60817
129.151893.513963.8631559.301576.0109938.005540.5182640.20416
110.905275.8374976.977962.43763129.093136.1209344.6014934.23636
138.275191.5181874.4119776.977988.5747936.4350241.7746433.29407
107.48492.0883879.2587357.87598136.003143.973339.5759732.97998
94.0841190.6628782.1097655.59515100.196345.5437837.0632133.60817
88.9522585.245979.5438357.87598129.721231.723638.005543.9733
98.6457678.6885280.3991470.9907388.5747945.2296851.5115833.60817
118.888193.513965.2886774.41197114.958834.2363640.2041632.35179
Mean10086.2556473.4259963.6730810036.2779738.6336934.17092
SD15.278127.1307968.0744438.43018819.061564.1130653.831222.947897
Table 2

Tumor volume changes in itraconazole, paclitaxel and the two in combination treatment groups in the HT-29 tumor-bearing nude mice.

ITCZ (10 mg/Kg), PTX (20 mg/Kg)
ITCZ (20 mg/Kg), PTX (20 mg/Kg)
Daysmice 1mice 2mice 3mice 4MeanSDmice 1mice 2mice 3MeanSD
Control

127.3266676.2823.8116732.4550417.4683412.8175941.44873.47657.77657.5666716.01503
1310.466679.4250.2456.5231.6616725.2125212.421367.38301.44293.74777.76541
1415.725.1294.2161.186774.0516767.81762233.4716353.4824320.28302.411361.96867
1551.02537.68234.4533314159.2896136.7419273.9367519.042512.8667435.2818139.763
1653.145.2345.45472.1228.9625213.9949433.3828574.62586.1333531.378785.06197
1755.2770858.61333444.8333518.1269.2059246.9197565.2746.0483653.12654.789490.43571
1864.1083387.92549.5636.1117334.41300.6149653.12775.58707.5467712.082261.35586
19100.48175.84765.375986.4833507.0446436.4964583.569817.4456774.8997725.3048124.5765
20139.2067233.5375769.31260.187600.5577519.9785521.4619803.1492820.482715.031167.8597
21139.2067301.44807.7651289.493634.4763521.3065582.1649895.2564912.798796.7398186.0342
22139.2067301.441036.21549.59756.6092657.1034605.29731148.0631033.256928.872286.043
23167.4667334.93331408.291604.933878.9056732.4421--1285.831285.83-
24244.6583835.241387.881921.681097.365721.0438--1603.3631603.363-
25287.8333875.01331730.9252197.4771272.812855.0437--1584.2091584.209-
26366.33331122.552373.842197.4771515.05944.6044--1738.8981738.898-

ITCZ

1215.5628217.2017425.3930420.0231919.54524.31187824.282.6866730.245.6955632.17541
1338.4877525.4840635.0405840.9565234.992236.78722224.0733383.7333332.2373346.6813332.34657
1461.2340.9565273.7217465.5304360.3596713.9346324.59667178.770754.070885.8127181.84172
15112.580451.19565127.4203145.6232109.204940.9656726.16667252.037369.0643115.7561119.9562
1699.79267.32609167.2826244.5826144.745878.506831.92333256.53893.0696127.177116.1267
1798.2956585.09855232.087307.1739180.6638107.341228.3542279.2088106.132137.8983128.4088
18102.3913112.1754294.887384.0565223.3775138.966338.4336320.28122.46160.3912144.7012
19113.8079196.5913432.6033443.0659296.5171166.697136.4554521.0935124.9092227.486258.0892
20152.0511213.9978496.9391482.7174336.4264179.0237-546.3077126.1338224.1472286.0384
21170.8885281.5761552.913498.6087375.9966180.109-599.0283163.414254.1474309.65
22250.5401309.3924611.6174536.1333426.9208174.1295-664.738200.2818432.5099328.4202
23264.3061324.1254611.6174846.0072511.514269.6496-678.24235.5456.87313.0645
24364.422418.6667728.1159989.2812625.1214290.8653-819.54317.9878568.7639354.651
25470.1695450.5217767.93481290.952744.8945391.9349-836.81328.9307582.8704359.1249
26585.6783691.7101804.56811783.725966.4203552.1512-881.712-881.712-

PTX

1220.415.96620.347227.47518.549559.031467111.538528.88821.9854.1354949.83228
1349.4559.4226.1666750.2433.8204219.73156140.897433.4514746.15873.502358.71066
1461.24526.1666754.95102.0561.0555638.30833163.843627.00485.973292.273668.63701
1570.9244.2216765.94102.0570.7372229.21111163.843624.8897381.388890.0407169.87979
1691.21447.2585.62142.3191.7266747.82331163.843621.885881.388889.039471.28746
17113.12451.28667102.5733184.2133112.691167.03843252.488220.9333379.1437117.5217120.4536
18131.58765.94102.5733230.2667132.926786.26591270.523120.9333379.1437123.5334130.5817
19151.62565.94150.72240.7333152.464487.40972337.308522.419673.86745144.5318168.9196
20-76.93167.4667251.2165.198987.15713337.308520.9333366.67267141.6382170.9917
21-76.93157294.375176.1017109.9738346.945823.4034766.67267145.674175.644
22-76.93244.6583306.15209.2461118.6422388.172424.96355.27708156.1375201.519
23-76.93336.765353.25255.6483154.9939307.7222.859247.77353126.1176157.7649
24-116.7688586.1333512.8667405.2563252.509256.53821.7706741.5422106.617130.2112
25-117.2267777.15615.44503.2722343.9635233.580617.7933336.4344795.93612119.5674
26-146.5333967.12703.36605.6711418.9248141.702618.463236.4344765.5334166.57362

ITCZ+PTX

1215.24738.00721.2473317.6886715.647676.44528970.6529.3066751.2866750.4144420.68546
1328.6533323.3864628.2637.6829.775499.610885444.833329.3066771.435181.8583228.7151
1478.922551.2866771.435119.058380.5933334.80167316.51239.56476.5375144.2045150.3634
15114.158.61333117.75164.85113.737853.23186359.467225.9573373.476152.9668180.4059
16147.397562.31180.625192.81145.248372.08463349.48225.1266.882147.1613176.4547
17169.208369.60333207.9596226.865168.142685.85948326.08931.148866.882141.3733160.9632
18192.599884.51833240.21253.555192.761193.97817321.22235.042461.544139.2695158.1317
19204.818898.125240.21268.47202.268391.29092316.35528.4860848.56533131.1355160.7187
20218.0813104.6667268.47282.6218.578998.90354224.133217.081643.6852594.96668112.6496
21230.8758104.6667313.215274.75230.8772110.9807178.226410.9020833.7445374.29190.7324
22155.43304.9725311.3833257.261988.24729178.22646.2832.4466772.3176992.64807
23172.7366.3333313.215284.0828100.0499168.80644.29133331.468.1659188.20488
24207.24387.79366.3333320.454498.63179158.2564.29133324.4637462.3370283.67837
25219.8397.7333375.0338330.855796.84443148.62673.97733322.5033358.3691178.71228
26248.5833492.195471403.9261134.9475125.86173.97733321.9850.6063365.7917
Fig. 1

Histopathologic findings of liver tissue A: Itraconazole (20 mg/Kg) group B: Itraconazole (20 mg/Kg) + Paclitaxel (20 mg/Kg) group. Hepatic cells showed increased inflammatory cells in itraconazole + paclitaxel groups but were only lower than those in itraconazole 20 mg / kg. H&E staining, Magnification: 40×, Scale bar: 100µm.

Table 3

The 99mTc- MIBI accumulation in vital organs of HT-29 xenograft nude mice (n= 3 for each group).

Injection Dose= (Total-Tail-Syring):253967525287792012263
ControlWeight of organsCpm%CPM/ID*W (except intestine: %Cpm/ID)MeanSD
blood0.510.4070.6811727307158790.1333350.2983830.4290140.28690.1482
heart0.130.2280.13358559942463347917.7366716.3462112.5093915.53082.7074
s.a0.1360.1790.1141391018707105354.0272634.132764.5924544.25080.3005
lung0.2390.160.14214363724787952.3662961.7911313.0779582.41180.6446
liver0.7240.8660.83218927326491117463810.2937112.0968210.4311110.94051.0037
kidney0.3340.3810.26432448337450516458338.2531638.8706430.9810636.03504.3877
spleen0.1490.130.08911843968373793.1296612.9454774.1202423.39850.6318
stomach0.2770.2710.2412170312567177593.0850471.8337983.6619862.86030.9346
muacle0.1560.1580.1927019804780191.7716282.014032.0755551.95370.1607
bone0.0420.1110.3321859417576731.7428171.4873821.148531.45960.2981
tumor2.4060.3812.809118999136131312591.9474641.4129212.3221621.89420.4570
intestine---53731147297940635521.1566818.7038520.1939320.01821.2358
tail---5456371459482891-----
syringe---177479171479276563-----
ITCZInjection Dose= (Total-Tail-Syring)209370725895952037811
blood0.1840.2380.4244131439930471.0723130.7137480.3526490.71290.3598
heart0.180.1520.0833612341303246029.58507110.4931614.5454911.54122.6411
s.a0.1040.120.10385839455100073.9417563.0426254.7676323.91730.8628
lung0.1630.1150.1197403489547752.1692231.6437011.9690761.92730.2652
liver0.9391.11.07425261141348327244712.8490414.5155412.4484113.27101.0963
kidney0.2930.3520.21716486627426010099126.8749430.0876222.8380526.60023.6326
spleen0.1290.1050.07310463638352673.8739192.3474893.5405973.25400.8026
stomach0.3020.3840.189181192488793952.8655722.5027042.4393322.60250.2300
muacle0.1670.2720.08581911433932032.3426342.035721.8491582.07580.2492
bone0.2160.1050.1937015603584911.5511652.2195052.1589251.97650.3696
tumor4.6192.9751.567263219170831674752.7217822.2174192.1130512.35080.3255
intestine---54619960731947930326.0876523.4522723.5204824.35351.5022
tail---49731539551608699-----
syringe---180695142571125207-----
PTXInjection Dose= (Total-Tail-Syring)259259526560272231159
blood0.3370.1810.1694679354430.0534510.1944910.1174860.12180.0706
heart0.150.1290.1422121532003192045.455289.3404646.0613976.95242.0902
s.a0.150.1360.11213023985194043.3487682.7271493.7632583.27970.5215
lung0.120.1360.1836071628770801.9513911.7404921.734011.80860.1237
liver1.0771.2811.0782027951819911542807.2628455.3489466.4144626.34210.9590
kidney0.2560.320.28315646716819111657723.574819.7888318.4627320.60882.6528
spleen0.0280.0790.1421859453846382.5608652.1627431.4639012.06250.5553
stomach0.160.2760.2621090714195113802.6293631.9363941.9467512.17080.3971
muacle0.1870.2120.278989511003121712.0409831.9540821.9622341.98580.0480
bone0.2140.2360.255110631544362671.9939972.4636961.1015111.85310.6919
tumor0.1820.91.015449834811288450.9532641.4562681.273721.22780.2546
intestine---53811564480449953820.7558424.2770122.3891722.47401.7621
tail---6451116307237918.3-----
syringe---11461199383302639.7-----
ITCZ+PTXInjection Dose= (Total-Tail-Syring)254483521929712455027
blood0.0560.1040.1492040335065631.4314711.4688541.7941541.56480.1995
heart0.1440.1920.14948755558285150413.3044513.2592214.0798613.54780.4613
s.a0.1310.1640.0972077727709117396.232357.7044934.9295026.28881.3884
lung0.1130.140.189102718399160193.5716972.7356883.4523693.25330.4522
liver0.841.1391.02525763823491025747112.052339.40469710.2317110.56291.3545
kidney0.2270.2510.32513471312229118425523.3197522.2171223.0929622.87660.5823
spleen0.0870.1540.168719910271115433.2515713.0412982.7986793.03050.2266
stomach0.2010.1690.5141713512715270953.3498733.430812.1471862.97600.7189
muacle0.3480.090.523151994743244751.7162322.4031321.9061832.00850.3547
bone0.370.1551.094147237223554391.5636332.1249712.0641521.91760.3080
tumor0.7331.3930.76893935115540704095.0357453.7822333.7343124.18410.7379
intestine---55097154131579427921.6505624.6840932.3531626.22935.5161
tail---4383541819946031-----
syringe---183047160547270659-----
The in vitro cell cytotoxicity of itraconazole alone, paclitaxel alone and itraconazole+ paclitaxel co-treatment in YM-1 and HT-29 cell lines. Tumor volume changes in itraconazole, paclitaxel and the two in combination treatment groups in the HT-29 tumor-bearing nude mice. The 99mTc- MIBI accumulation in vital organs of HT-29 xenograft nude mice (n= 3 for each group).

Experimental Design, Materials and Methods

MTT assay test

Human colorectal cancer cell line (HT-29) and Human ovarian cancer cell line (SKOV3) cultured in RPMI and DMEM medium supplemented with 10% fetal bovine serum and penicillin-streptomycin at 37°C and 5% CO2. Then these cells were seeded in 96-well plates and respectively incubated with 200 µl of RPMI and DMEM at 37°C for 24 h, again. After incubation, the medium was removed and cells were treated with paclitaxel (0.05μM), itraconazole (5μM), and combination treatment of itraconazole (5μM) + paclitaxel (0.05μM). It is notable that 104 cells were seeded in each well and the total dishes for each group were 24. After 48 and 72 h incubation, 20 µL of MTT solution (5mg/ml) was added to each well and incubated at 37°C for 4 hours, again. Then, the supernatant was removed and 100 µL of DMSO was added and mixed slowly. Finally, the absorbance of plates was read on an ELISA reader at a wavelength of 570 nm (Biotech, USA). The untreated cells (24 dishes) were used as a control group to compare cell absorbance and survival. The cell survival percentage was calculated according to following equation: Live cell percentage (%) = (absorption of treated / absorbed control cells) × 100%.

Effects of itraconazole and paclitaxel and their co-administration on tumor growth in HT-29 xenograft nude mice

HT-29 cells (1 × 107) suspended in 100 μl fresh medium and subcutaneously administerd into the right hind legs of the mice using a grafting needle. The first tumor sizes were measured 12 days after transplantation by external vernier caliper and to assess the anti-tumor effects of itraconazole, paclitaxel and their contaminant treatment, the tumor volumes daily recorded till the end of treatment period. The tumor volume was calculated according to the standard formula (length × width × height × π)/6) [10]. Also, 12 days after transplantation the tumor-bearing nude mice were divided uniformly based on tumor volume into 4 experimental groups: The first treatment schedule was control group, itraconazole group (20 mg/Kg, i.p), paclitaxel group (20 mg/Kg, i.p), itraconazole (20 mg/Kg, i.p) + paclitaxel (20 mg/Kg, i.p) group. Itraconazole-induced liver toxicity at dose of 20 mg/Kg caused to decrease the dose of itraconazole to 10 mg/Kg. The second treatment schedule was control group, itraconazole (10 mg/Kg, i.p), paclitaxel (20 mg/Kg, i.p), itraconazole (10 mg/Kg, i.p) + paclitaxel (20 mg/Kg, i.p) group. The treatment protocol was started 14 days after HT-29 cells transplantation and drugs were injected intraperitoneally on 14th, 18th, 22th, and 26th days for a total of 12 days of treatment period. It is noted that itraconazole was injected 30 min before paclitaxel administration. Histopathologic findings of liver tissue A: Itraconazole (20 mg/Kg) group B: Itraconazole (20 mg/Kg) + Paclitaxel (20 mg/Kg) group. Hepatic cells showed increased inflammatory cells in itraconazole + paclitaxel groups but were only lower than those in itraconazole 20 mg / kg. H&E staining, Magnification: 40×, Scale bar: 100µm.

99mTc-MIBI biodistribution pattern

24 hours after the final drug injection, 99mTc-MIBI (10MBq in 0.1 ml) was intravenously injected to through the tail vein and mice were killed with a lethal dose of ketamine/xylazine (i.p.) at 60 min after 99mTc-MIBI injection. Then blood was collected and necessary organs such as heart, lung, liver, spleen, salivary gland, stomach, kidney, muscle, bone, and tumor were removed, weighed and their radioactivity was counted by a gamma counter. 99mTc-MIBI uptake values were calculated as a percentage of injected doses per gram of tissue (%ID/g) except for intestine (%ID).

Statistical analysis

Data were analyzed using Excel and Graph Pad Prism 6 software (Graph Pad, La Jolla, CA, USA) and statistical analysis was done by ANOVA and independent-samples T-test.

Ethics Statement

The authors confirm that all experiments comply with the ARRIVE guidelines and were carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments, or the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978)]. Also, ethical aspect of the research such as animal keeping and the minimum number of nude mice that needed for valid statistical analysis approved by the Research Ethics Guidelines of Mazandaran University of Medical Sciences.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper
SubjectHealth and medical sciences
Specific subject areaIn vitro and in vivo anti-cancer effect of itraconazole, paclitaxel and the two in combination in YM-1 and HT-29 cell lines and HT-29 colon cancer xenograft models.
Type of dataTableFigure
How data were acquiredELISA reader (Biotech, USA), Gamma counter with a NaI (Tl) detector ((Delshid, Tehran, Iran)Excel 2016, Graf pad prism 8
Data formatRaw analyzed
Parameters for data collectionCytotoxic effects of paclitaxel, itraconazole and concomitant treatment in Human colorectal cancer cell line (HT-29) and esophageal cancer cell line (YM-1) lines were evaluated by MTT test. cell viability % percentage was obtained through following equation: Absorption of Treated / Absorbed Control Cells) × 100%. In vivo anti-tumor efficacy of paclitaxel, itraconazole and their synegestic effect was illustrate by measurment of tumor volum by external vernier caliper during the 12 days’ treatment period. P-gp medulatory effect of itraconazole also assessed by biodistribution pattern of 99mTc-MIBI in HT-29 xenograft model, too.
Description of data collectionHuman colorectal cancer cell line (HT-29) and esophageal cancer cell line (YM-1) were seeded in 96-well plates with 200 µl of RPMI and DMEM medium and incubated at 37°C for 24 h. Afret that, the medium was removed and cells were exposed to paclitaxel alone (0.05μM), itraconazole alone (5μM), and the two in combination (itraconazole + paclitaxel) with the same concentrations (n=24). After 48 and 72 h incubation, 20 µL of MTT solution (5mg/ml) was added to the each well and incubated at 37°C for 4 hours. Then, the supernatant was removed and 100 µL of DMSO was added and absorbance of plates were read on an ELISA reader at a wavelength of 570 nm.For animal study, 1 × 107 cell of HT-29 cell line were subcutaneously injected into the right hind legs of the Twenty-four female nude mice (3 to 5-week-old, 14-20 g). when tumors appeared, they divided to some extent uniformly based on tumor size into 4 following experimental groups. Control group, itraconazole group (10 mg/Kg, i.p), paclitaxel group (20 mg/Kg, i.p), itraconazole (10 mg/Kg, i.p) + paclitaxel (20 mg/Kg, i.p) group. The daily tumor size measurment was started on 12th days after HT-29 cell transplantation and cotinued untill the end of the treatment period.The treatment schedule was started on 14 th day and drugs were injected intraperitoneally on 14th, 18th, 22th, and 26th days after HT-29 cells transplantation.Sestamibi kit (MIBI) was prepared according to the manufacturer's protocol and intravenously injected through the tail vein of nud mice 24 hours after final treatment day. 60 min after radiotracer injection, mice were sacrificed with a lethal dose of ketamine/xylazine (i.p.) and blood collected and other organs ranging from heart and liver to tumor were removed, weighed and counted by a gamma counter.
Data source locationInstitution: Mazandaran University of Medical SciencesCity/Town/Region: Sari, FarahabadCountry: Iran
Data accessibilityData is with this article.
Related research articleMahdi Ghadia, Seyed Jalal Hosseinimehra, Fereshteh Talebpour Amirib, Alireza Mardanshahic, Zohreh Noaparasta*, Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulationin in HT-29 tumor-bearing nude mice, European Journal of Pharmacology,https://doi.org/10.1016/j.ejphar.2021.173892
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