Da-Long Wu1, Ying Xu, Li-Xin Yin, Huan-Zhang Lu. 1. Department of Pharmacology, School of Medicine, Jiaxing College, Jiaxing 314001, Zhejiang Province, China. wudalong66@sina.com
Abstract
AIM: To investigate the reversal effect of LY980503, a benflumetol derivative, on multidrug resistance in vincristine (VCR) -resistant human gastric carcinoma cell line SGC7901/VCR. METHODS: Cells of a human gastric cancer cell line, SGC7901, and its VCR-resistant variant, SGC7901/VCR, were cultivated with LY980503 and /or doxorubicin (DOX). The cytotoxicity of drugs in vitro was assayed by MTT method. Based on the flow cytometric technology, the uptake of DOX was detected in these cells by measuring DOX-associated mean fluorescence intensity (MFI). RESULTS: SGC7901/VCR cells were 23.5 times more resistant to DOX in comparison with SGC7901 cells. LY980503 at the concentrations of 2.0 micromol/L-10 micromol/L had no obvious cytotoxicity to SGC7901 and SGC7901/VCR cells. After simultaneous treatment with LY980503 at the concentrations of 2.0, 4.0 and 10 micromol/L, the IC(50) of DOX to SGC7901/VCR cells decreased from 1.6 +/- 0.12 micromol/L to 0.55 +/- 0.024, 0.25 +/- 0.032 and 0.11 +/- 0.015 micromol/L, respectively, thus, increasing the DOX sensitivity by 2.9-fold (P < 0. 05), 6.4-fold (P < 0. 01) and 14.5-fold (P < 0. 01), respectively. In the uptake study of DOX, simultaneous incubation of SGC7901/VCR cells with LY980503 significantly increased the DOX -associated MFI in SGC7901/VCR cells. No such results were found in parental SGC7901 cells. CONCLUSION: LY980503 at non-cytotoxic concen-trations can effectively circumvent resistance of SGC7901/VCR cells to DOX by increasing intracellular DOX accumulation.
AIM: To investigate the reversal effect of LY980503, a benflumetol derivative, on multidrug resistance in vincristine (VCR) -resistant humangastric carcinoma cell line SGC7901/VCR. METHODS: Cells of a humangastric cancer cell line, SGC7901, and its VCR-resistant variant, SGC7901/VCR, were cultivated with LY980503 and /or doxorubicin (DOX). The cytotoxicity of drugs in vitro was assayed by MTT method. Based on the flow cytometric technology, the uptake of DOX was detected in these cells by measuring DOX-associated mean fluorescence intensity (MFI). RESULTS: SGC7901/VCR cells were 23.5 times more resistant to DOX in comparison with SGC7901 cells. LY980503 at the concentrations of 2.0 micromol/L-10 micromol/L had no obvious cytotoxicity to SGC7901 and SGC7901/VCR cells. After simultaneous treatment with LY980503 at the concentrations of 2.0, 4.0 and 10 micromol/L, the IC(50) of DOX to SGC7901/VCR cells decreased from 1.6 +/- 0.12 micromol/L to 0.55 +/- 0.024, 0.25 +/- 0.032 and 0.11 +/- 0.015 micromol/L, respectively, thus, increasing the DOX sensitivity by 2.9-fold (P < 0. 05), 6.4-fold (P < 0. 01) and 14.5-fold (P < 0. 01), respectively. In the uptake study of DOX, simultaneous incubation of SGC7901/VCR cells with LY980503 significantly increased the DOX -associated MFI in SGC7901/VCR cells. No such results were found in parental SGC7901 cells. CONCLUSION:LY980503 at non-cytotoxic concen-trations can effectively circumvent resistance of SGC7901/VCR cells to DOX by increasing intracellular DOX accumulation.
Authors: Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du Journal: World J Gastroenterol Date: 2004-06-15 Impact factor: 5.742