Research on Apoptosis of (-)-gossypol to Murine Cervical Cancer Xenograft and Its Mechanisms

Objective To investigate the role of (-)-gossypol on apoptosis of murine cervical cancer xenograft induced by Cisplatin and its possible mechanisms.Method To establish sixty models of subcutaneous xenograft of cervical cancer U14 cells on Kunming mice,then divide them into 4 groups randomly,which were LGP group,LGP+DDP group,DDP group and model control group,respectively.The groups were under continuous medication intervention for 8 days,then the mice were euthanasiaed after medication intervention(2 day),the xenograft was exfoliated,the tumors′ weight was weighed and the inhibition rate of tumor was calculated;the apoptosis of tumor cells was detected by TUNEL and the apoptosis index (AI) of each group was calculated;the apoptosis-related protein expression level(Bcl-2,Bax) and resistance-associated protein expression level(P-gp) of tumor tissue in each group were detected by immunohistochemistry. Results The weight of tumor in model group were higher than that in other three groups,the weight of tumor in LGP+DDP group was the lowest(P<0.01),and the lighter group was DDP group.The AI in experimental group was higher than that in model group,and the AI in LGP+DDP group was the highest (P<0.01);the expression of P-gp and Bcl-2 protein in LGP and LGP+DDP group was decreased (P<0.05),the expression of Bax protein and the rate of Bax/Bcl-2 were increased(P<0.05);there was positive correlation between the expression of P-gp and Bcl-2,as well as,negative correlation between the expression of P-gp and Bax (P<0.01). Conclusion LGP could inhibit the growth of the transplanting tumor of murine cervical carcinoma U14,and modality therapy was more efficiency when combined with DDP;LGP can induce apoptosis by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein,and enhance the chemotherapy sensitivity by decreasing the expression of P-gp protein.