Chunying Li, Jinhai Zou, Guoqi Zheng, Jiankun Chu
Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland)
Med Sci Monit 2016; 22:4509-4515
Available online: 2016-11-22
The effectiveness of chemotherapy for gastric cancer is largely limited by either intrinsic or acquired drug resistance. In this study, we aimed to explore the association between miR-30a dysregulation and multidrug resistance (MDR) in gastric cancer cells.
MATERIAL AND METHODS: We recruited 20 patients with advanced gastric cancer. Chemosensitivity was assessed after completion of the chemotherapy. SGC-7901 and SGC-7901/DDP cells were transfected for miR-30a overexpression or knockdown. Then, MTT assay was performed to assess the IC50 of DPP and 5-FU in SGC-7901 and SGC-7901/DDP cells. Flow cytometry analysis was used to detect DPP- and 5-FU-induced cell apoptosis. Western blot analysis and immunofluorescence staining were used to assess EMT of the cells.
RESULTS: MiR-30a was significantly downregulated in the chemoresistant tissues. In both SGC-7901 and SGC-7901/DDP cells, miR-30a overexpression decreased the expression of P-gp, a MDR-related protein. MTT assay and flow cytometry analysis showed that miR-30a inhibition increased chemoresistance, while miR-30a overexpression decreased chemoresistance in gastric cancer cells. Both Western blot analysis and immunofluorescence staining confirmed that miR-30a inhibition decreased E-cadherin but increased N-cadherin in SGC-7901 cells, while miR-30a overexpression increased E-cadherin but decreased N-cadherin in SGC-7901 cells.
CONCLUSIONS: MiR-30a can decrease multidrug resistance (MDR) of gastric cancer cells. It is also an important miRNA modulating EMT of the cancer cells.
Keywords: Apoptosis - drug effects, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Cadherins - metabolism, Cell Line, Tumor, Cell Proliferation - drug effects, Cisplatin - administration & dosage, Down-Regulation - drug effects, Drug Resistance, Neoplasm - genetics, Epithelial-mesenchymal transition, Fluorouracil - administration & dosage, Gene Knockdown Techniques, MicroRNAs - genetics, Stomach Neoplasms - pathology, Transfection