The Role Of Autophagy In Cispeatin-resistant Cell Death Induced By Paclitaxel In Human Ovarian Cancer

Non operation therapy of tumor, its purpose is to reduce the energysupply in most tumor cells, the tumor residual in the metabolic stressbecome fragile, so if the protective effect of inhibiting autophagy, tumorcells will be unable to timely and effective response to metabolic stressand death. The present study shows that, many kinds of chemotherapeuticdrugs can induce autophagy, including paclitaxel (Paclitaxol, PTX),doxorubicin, cyclophosphamide, topotecan gemcitabine (topotecan, TPT)etc…[5,6]Research has shown that, targeting lysosomal drug chloroquine(chloroquine, CQ) could inhibit autophagy, promote[7]killing effect ofchemotherapy drugs on tumor cells. However, the autophagy induced bychemotherapy drugs is to promote or inhibit tumor cell death, is not clear.Because both sides of the autophagy.Purpose: Use of chloroquine, the autophagy inhibitor, to investigatethe role of autophagy in paclitaxel (Paclitaxol, PTX) inducedcisplatin-resistant human ovarian cancer cell (SKOV3/DDP) death in theprocess.Method: The inhibition effect of different concentration of PTX onSKOV3/DDP cells proliferation was detected by using MTT method. Toobserve the survival of SKOV3/DDP cells under phase contrastmicroscope; and the expression of autophagy-related protein LC3, ATG-12and P-JNK by immunoblotting detection. Application of SPSS16.0software to process data, count data using X2test correlation analysis. P <0.05indicates significant difference.Result:①The MTT results showed that, different concentrations of PTX in SKOV3/DDP cells after24h, with the increase of PTXconcentration, cell survival rate decreased, in a dose-dependent manner.Compared with the single application of PTX, after the combination ofCQ, SKOV3/DDP were significantly decreased cell survival;②Observedby microscope the number of viable cells obviously reduced;③Westernblot shows, the expression of autophagy related proteins LC3, ATG12andapoptosis related protein P-JNK was up-regulated.Conclusion:1、Autophagy may play against death in the process of PTX inducedin cisplatin-resistant human ovarian cancer cell death.2、Autophagy demonstrated against death effect, may be one of themechanism of tumor multidrug resistance.3、Inhibition of autophagy may be a new strategy to improve theeffect of chemotherapy.