The relationship between autophagy and the sensitivity to cisplatin in ovarian cancer SKOV3 and SKOV3/DDP cells / 肿瘤

ABSTRACT

Objective: To investigate the relationship between the autophagy and the sensitivity to DDP (cisplatin) in epithelial ovarian cancer SKOV3 and SKOV3/DDP cells. Methods: The formation of autophagosomes in SKOV3 and SKOV3/DDP cells was observed under a TEM (transmission electron microscope). MTT assay was used to screen the dose of nontoxic reaction of autophagy inhibitor 3-MA (3-methyladenine) and to examine the sensitivity to DDP in SKOV3 and SKOV3/DDP cells after treatment with the combination of DDP and 3-MA. The apoptotic rate and the expressions of autophagic marker protein LC3 (microtubule-associated protein 1 light chain 3) and autophagy-related protein Beclin1 in SKOV3 and SKOV3/DDP cells after treatment with DDP and 3-MA alone and the combination of DDP and 3-MA were detected by flow cytometry and Western blotting, respectively. Results: Much more autophagosomes in SKOV3/DDP cells were observed as compared with that in SKOV3 cells. As compared with DDP treatment alone, when DDP was used in combination with 3-MA, the IC50 (half inhibitory concentration) value of DDP for SKOV3/DDP cells was decreased from (17.71±0.15) μg/mL to (8.85±0.11) μg/mL (P < 0.05), and the apoptotic rate was increased from (6.93±0.94) % to (14.82±0.85) % (P < 0.05), as well as the expression levels of LC3 and Beclin1 proteins in SKOV3/DDP cells were significantly decreased (P < 0.05), but there were no significant changes could be observed in SKOV3 cells. Conclusion: The increased activity of autophagy is related to DDP-resistance of ovarian cancer cells. The inhibition of autophagy may enhance the sensitivity to DDP in SKOV3/DDP cells. Copyright © 2013 by TUMOR.