Effects Of SAHA Alone Or Combined With PTX On Survival And Autophagy Of Human Ovarian Cancer OC3 Cells

Ovarian cancer is one of the common gynecological malignant tumors,and it has been still depended on the surgery and chemotherapy as the main treatment methods. Paclitaxel(PTX) is the first choice basic chemotherapy drug in the treatment of ovarian cancer because it was found to cause tumor cell autophagy in addition to inhibiting tumor. At present, the treatment of epithelial ovarian cancer is treated with paclitaxel combined with platinum drugs, but platinum drugs always affect the treatment of ovarian cancer.Therefore, the combination therapy with the PTX has become the focus in the field of ovarian cancer treatment.Suberoylanilide hydroxamic acid(SAHA) is one of the histone deacetylase inhibitor(HDACI), which is now the most representative HDACI drug. It was reported that SAHA induced the HDAC abnormal expression to act anti-tumor role. Besides of effects on many solid tumors and hematological malignancies, combining with a variety of chemotherapy drugs, SAHA can play a synergistic effect and induce cell differentiation, apoptosis and autophagy. Recent studies showed that the emerge and development of tumors have closely related to autophagy. In this study, the effects of SAHA and SAHA combined with PTX on lethal and autophagy of human ovarian cancer OC3 cells are observed to provide some experimental evidences for ovarian cancer treatment.Human ovarian cancer OC3 cells were cultivated, and the effects of SAHA and SAHA combined with PTX on inhibition of OC3 cell proliferation were tested with MTT. The morphology and ultrastructure changes of OC3 cells under drug treatment were observed with inverted microscope and transmission electron microscope and Giemsa staining method. The changes of autophagic vacuole between different treatmentgroups were detected with AO/EB double staining. Q- PCR was used to detect the expression pattern of cell autophagy-related gene ARHI and Beclin-1. Autophagy-related protein LC3 B was detected with flow cytometry, and autophagy protein Beclin-1 was detected with western- blot.The results showed that comparing with the SAHA、PTX treatment alone, SAHA with PTX had significant inhibiting effects on proliferation of human ovarian cancer cell OC3(P<0.05), and there was an obvious relationship of time and dose. Moreover, under the treatment of combined drugs, cellular morphology and ultrastructure changed significantly, and autophagosomes and autophagic vacuole increased. Q- PCR results showed that the expression of ARHI and Beclin-1 increased significantly with the treatment of combined drug. The expressing of LC3 B increased significantly(P<0.05) with the detecting of flow cytometry. The expression intensity of Beclin-1 was higher in the combined drug group.In a word, SAHA and SAHA combining with PTX can inhibit the proliferation of human ovarian cancer OC3 cell line and induce its autophagy, and the two drugs have synergistic antitumor effects.