Najibeh Shekari 1,2,3 , Faezeh Asghari 1,2 , Navideh Haghnavaz 1,2 , Dariush Shanehbandi 1,2 , Vahid Khaze 1 , Behzad Baradaran 1,2 , Tohid Kazemi 1,2 Show Affiliations »
Abstract
BACKGROUND: MicroRNAs are noncoding RNAs which play critical roles in response to anti-cancer agents. Let-7a and miR-21 are well-known tumor-suppressor and oncomiR miRNAs, respectively. They are involved in tumorigenesis of gastric cancer and have potential to be used as markers in response to the therapy. OBJECTIVE: We aimed to study alterations in the expression of Let-7a and miR-21, and their targets in gastric cancer cell lines after treatment with docetaxel. METHODS: In order to determine the IC50 of docetaxel, MTT assay was performed in AGS, MKN45 and KATO III gastric cancer cell lines. The expression levels of Let-7a and miR-21 and their target genes, HMGA2 and PDCD4, were determined by reverse-transcription quantitative real-time PCR for both treated and untreated cell lines. RESULTS: MTT assay showed higher IC50 concentration of docetaxel in KATO III in comparison with AGS and MKN45, indicating KATO III`s higher resistance to docetaxel. Following the treatment, the expression level of Let-7a was significantly increased in AGS and MKN45, while decreased in KATO III. Expression level of miR- 21 in the three treated cell lines was increased significantly. Not only Let-7a, but also expression level of HMGA2 and PDCD4 genes showed different patterns in KATO III in comparison with AGS and MKN45. CONCLUSION: Down-regulation and up-regulation of Let-7a in docetaxel-resistant and sensitive cell lines, respectively indicates its potential usefulness as biomarker for responsiveness of gastric cancer to the therapy with docetaxel and also for predicting patient`s outcome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
BACKGROUND: MicroRNAs are noncoding RNAs which play critical roles in response to anti-cancer agents. Let-7a and miR-21 are well-known tumor -suppressor and oncomiR miRNAs, respectively. They are involved in tumorigenesis of gastric cancer and have potential to be used as markers in response to the therapy. OBJECTIVE: We aimed to study alterations in the expression of Let-7a and miR-21 , and their targets in gastric cancer cell lines after treatment with docetaxel . METHODS: In order to determine the IC50 of docetaxel , MTT assay was performed in AGS , MKN45 and KATO III gastric cancer cell lines. The expression levels of Let-7a and miR-21 and their target genes, HMGA2 and PDCD4 , were determined by reverse-transcription quantitative real-time PCR for both treated and untreated cell lines. RESULTS: MTT assay showed higher IC50 concentration of docetaxel in KATO III in comparison with AGS and MKN45, indicating KATO III`s higher resistance to docetaxel . Following the treatment, the expression level of Let-7a was significantly increased in AGS and MKN45, while decreased in KATO III. Expression level of miR- 21 in the three treated cell lines was increased significantly. Not only Let-7a , but also expression level of HMGA2 and PDCD4 genes showed different patterns in KATO III in comparison with AGS and MKN45. CONCLUSION: Down-regulation and up-regulation of Let-7a in docetaxel -resistant and sensitive cell lines, respectively indicates its potential usefulness as biomarker for responsiveness of gastric cancer to the therapy with docetaxel and also for predicting patient `s outcome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Disease
Gene
Species
Keywords:
Gastric cancer; Let-7a; chemoresistance; chemosensitivity; docetaxel; miR-21.
Mesh： See more »
Substances： See more »
Year: 2019
PMID： 30543177 DOI： 10.2174/1871520619666181213110258
Source DB: PubMed Journal: Anticancer Agents Med Chem ISSN： 1871-5206 Impact factor: 2.505