Effect of siRNA targeting MACC1 gene on chemoresistance to cisplatin in ovarian cancer / 肿瘤

ABSTRACT

Objective: To knock down the expression of metastasis-associated in colon cancer-1 (MACC1) gene in drug-resistant ovarian cancer cell line SKOV3/cisplatin (DDP) by RNA interference technology, and to investigate its effect on chemoresistance to DDP. Methods: Ovarian cancer SKOV3/DDP cells were not transfected (blank group, named as SKOV3/DDP cells), or transfected with empty plasmid (negative control group, named as SKOV-3/DDP-shVector cells) or combinant plasmid containing MACC1 specific small hairpin RNA (shRNA) (experimental group, named as SKOV-3/DDP-shMACC1 cells). The mRNA and protein expressions of MACC1 were detected by reverse transcription-PCR (RT-PCR) and Western blotting, respectively. The half inhibition concentration (IC 50) of DDP was determined by MTT assay. The apoptosis was examined by flow cyometry. Results: After transfection of MACC1 shRNA into SKOV-3/DDP cells, the expressions of MACC1 mRNA and protein obviously decreased by (83.39±1.26)% and (82.25±2.94)%, respectively, as compared with those of the blank group (P < 0.05). Compared with the blank group and the negative control group, the value of IC50 of DDP in SKOV-3/DDP-shMACC1 cells significantly decreased [(26.09±0.91) μmol/L vs (47.50±0.40) μmol/L and (47.08±0.45) μmol/L, P < 0.05]. The apoptotic rate of SKOV-3/DDP-shMACC1 cells was significantly higher than those in the SKOV-3/DDP-shVector cells and the SKOV-3/DDP cells [(1 3.77±0.60)% vs (4.23±0.30)% and (3.63±0.30)%, P < 0.05]. Conclusion: The sensitivity to DDP in ovarian cancer SKOV-3/DDP cells can be enhanced by inhibition of MACC1 gene expression induced by RNA interference. Copyright© 2014 by TUMOR.