The Effect And Mechanism Of Lysophosphatidic Acid On Cisplatin-Induced Apoptosis In Human Ovarian Carcinoma

Objective: Research indicated that the abnormal apoptosis of the cells is the important character of the cancer cells, at the same time, it is the most important reason for the beginning of the cancer, so resistance to apoptosis is an important factor in the survival of cancer cells. Along with the intensive study of the apoptosis of the cells, researcher began to know that most of the anti-cancer medicines brought about the effects by various ways of inducing apoptosis of sensitive cells. It had been reported that Lysophosphatidic acid (LPA) had dual action of survival and apoptogenic, but the exact mechanism is unknown. The purpose of this study was to investigate the effect of LPA on Cisplatin-induced apoptosis in ovarian carcinoma cells, and to give experimental basis for treating ovarian carcinoma.Methods: Human ovarian carcinoma cell line SKOV3 cells were cultured in intro, and Methyl thiazolyl tetrazolium (MTT) assay was used to examine the proliferative effect of Cisplatin (DDP) with or without LPA on SKOV3 cells. Flow Cytometry (FCM) was used to examine the effect of LPA on the apoptosis and cell cycle of SKOV3 cells treated with DDP. RT-PCR was performed to examine the expression of mRNA of Bcl-2,Bcl-xl and Bax,Bad in human ovarian epithelial serous cancer cell line SKOV3 treated with LPA.Results: Cisplatin could inhibit the growth of SKOV3 cells effectively, in a dose-dependent pattern. In addition, DDP could cause a significant G0-G1 phase arrest with concurrent decreasing of S phase in SKOV3 cells, compared with the control cells. Pretreatment of LPA suppressed DDP-induced apoptosis when LPA was applied to cultured SKOV3 cells with different concentrations. The percentage of G0/G1-phase cells was decreased by different concentrations of LPA. The specific DNA"ladder"pattern for apoptotic cells couldn't be found in which the cells were exposed to LPA. The expression of Bcl-2 family was analyzed by semi-quatitive RT-PCR. Stimulation with DDP resulted in decrease in Bcl-2 mRNA level. LPA were found to up-regulate Bcl-2 mRNA and down-regulate Bax mRNA, but LPA had no effect on the expression of Bcl-XL mRNA and Bad mRNA.Conclusions: LPA could protect the apoptosis induced by DDP and the mitochondrial pathway was involved in the anti-apoptotic effect of LPA. It's also suggests that LPA may be an important chemoresistent reason for the chemotherapy of ovarian cancer. Critical tools, such as gene knockout, gene down regulation using the small inference RNA technology, and specific agonists or antagonists for lipid and GPCR maybe improve the curative effect of DDP and make a significant improvement in cure rates.