Drug resistance is one of major obstacle that reduce the effectiveness of Drug resistance is one of major obstacle that reduce the effectiveness of chemotherapy of ovarian cancer, via requiring novel therapeutic strategies that could induce the respon...
Drug resistance is one of major obstacle that reduce the effectiveness of Drug resistance is one of major obstacle that reduce the effectiveness of chemotherapy of ovarian cancer, via requiring novel therapeutic strategies that could induce the response to the anti cancer reagents. Recently, the induction of autophagy has been suggested as a tool that could overcome the drug resistance of cancer cells. Combined treatment of autophagy activator with some drugs induced chemo sensitivities by reducing cell viability or inducing apoptosis in several cancer types, particularly those which are platinum-based drugs. However, there are not yet results that clearly show the ability of autophagy to overcome of drug resistance of ovarian cancer cells. The aim of this study is to estimate the therapeutic effects of the regulation of autophagy on the drug resistant ovarian cancer cells. We estimated the expression of LC3-2 and p62, defined components of autophagy mechanism in drug resistant ovarian cancer cell lines and compared them with those in individual parent cell lines (drug sensitive cell lines). We pretreated autophagy regulator, chloroquine (CQ) at ovarian cancer cells and cells were incubated with cisplatin. Combined treatment of them mediated alteration of cell viabilities were estimated by MTT assay and the change of autophagy was through estimation of protein expression levels of them by Western blotting assay using specific antibody against them. We found that both LC3-2 and p62 were relatively down-regulated in drug resistant ovarian cancer cells. Pretreatment of CQ increased the response to the cisplatin and bafilomycin induced reverse results. Moreover, we identified that single treatment of CQ reduced cell viability and combined treatment of CQ and cisplatin increased the expression of both LC3-2 and p62 more efficiently than those by single treatment of either cisplatin or CQ in cisplatin resistant ovarian cancer cells. These results indicate the potential therapeutic strategy of the regulation of autophagy in ovarian cancer cells. Drug resistant ovarian cancer cells exhibited reduced expression of components of autophagy in comparison to their parent cells and combined treatment of autophagy regulator with cisplatin modified response to the cisplatin via reducing cell viability. Single treatment of cisplatin increased autophagy and increased cytotoxic effects when treated with autophagy activator. Therefore, our results show that induction of autophagy could be novel therapeutic strategy to overcome drug resistance of ovarian cancer cells.