关键词: 卵巢癌, 肿瘤坏死因子的相关凋亡诱导配体, 顺铂, 死亡受体, 细胞凋亡

Abstract: Background and purpose: The study has found that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can enhance the cytotoxic effect of chemotherapeutic drugs on tumor cells. The aim of our study was to investigate the effects of the tumor TRAIL and cisplatin combined application on the growth and apoptosis of human ovarian cancer cell lines SKOV3 and OVCAR3, and the possible mechanism. Methods: Under the combined application of cisplatin and TRAIL, MTT method and flow cytometry were used to detect the proliferation and apoptosis of SKOV3 of OVCAR3 cells; the mRNA expression levels of death receptors, DR4 and DR5, were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). At the same time, the protein expression levels of DR4 and DR5 were detected by Western blot. Results: SKOV3 and OVCAR3 cells were sensitive to TRAIL protein, and with the increasing of TRAIL protein concentration, cell growth inhibitory rate up to 64%. When the combination application of TRAIL and cisplatin, the inhibition rate of the two cells reached more than 92%, and the two drugs showed high synergistic effect, compared with the single drug group (P<0.05). Flowcytometry analysis indicated that the synergistic killing effect of TRAIL and cisplatin was mainly due to the cell apoptosis. RTFQ-PCR and Western blot detection results showed that the DR4 and DR5 were up-regulated under the combined application of TRAIL and cisplatin. Conclusion: In vitro, TRAIL and cisplatin combined application can significantly inhibit the proliferation of human ovarian cancer cells and induce tumor cell apoptosis. TRAIL can obviously enhance the sensitivity of cisplatin to tumor cells. The mechanism may be related to the increased death receptor DR4 and DR5 expression level.

Key words: Ovarian cancer, Tumor necrosis factor-related apoptosis inducing ligand, Cisplatin, Death receptor, Apoptosis