左旋棉酚对小鼠宫颈癌移植瘤细胞凋亡的影响及其机制

目的探讨左旋棉酚［(-)-gossypol,LGP］对顺铂诱导小鼠宫颈癌移植瘤凋亡的影响及可能的作用机制。方法建立小鼠宫颈癌U14细胞皮下移植瘤模型，将60只小鼠按随机原则分为左旋棉酚组、顺铂(Cisplatin,DDP)组、左旋棉酚+顺铂(LGP+DDP)组及模型对照（Model Control）组4组，用药干预8天后采用电子天平称量瘤重并计算抑瘤率;采用TUNEL法检测各组瘤组织的凋亡情况;采用免疫组织化学法检测各组肿瘤组织中Bcl-2、Bax和P-gp蛋白的表达水平。结果各干预组小鼠移植瘤瘤重均低于Model组，其中LGP+DDP组瘤重最低，其次为DDP组(P＜0.01);各组移植瘤组织内AI均高于Model组（P＜0.05），且LGP+DDP组最高（P＜0.01）;含LGP组移植瘤组织内P-gp、Bcl-2蛋白的表达降低（P＜0.05）， Bax蛋白的表达升高（P＜0.05），Bax/Bcl-2比值升高，LGP+DDP组的上述作用明显优于单药组（P＜0.01）;相关性分析表明P-gp蛋白的表达量与Bcl-2的表达量呈正相关，与Bax的表达量呈负相关（P＜0.01）。结论 LGP能抑制小鼠宫颈癌移植瘤的生长，且与DDP联合后抑制作用更显著;其可能的机制:LGP可能是通过下调Bcl-2、上调Bax蛋白诱导小鼠宫颈癌细胞凋亡，降低P-gp蛋白的表达，增加肿瘤组织对DDP的化疗敏感度。

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

ObjectiveTo investigate the role of (-)-gossypol on apoptosis of murine cervical cancer xenograft induced by Cisplatin andits possible mechanisms.Method To establish sixty models of subcutaneous xenograft of cervical cancer U14 cellson Kunming mice,then divide them into 4 groups randomly,which were LGP group,LGP+DDP group,DDP group and modelcontrol group,respectively.The groups were under continuous medication intervention for 8 days,then the mice wereeuthanasiaed after medication intervention(2 day),the xenograft was exfoliated,the tumors′ weight was weighedand the inhibition rate of tumor was calculated;the apoptosis of tumor cells was detected by TUNEL and theapoptosis index (AI) of each group was calculated;the apoptosis-related protein expression level(Bcl-2,Bax) andresistance-associated protein expression level(P-gp) of tumor tissue in each group were detected byimmunohistochemistry.ResultsThe weight of tumor in model group were higher than that in other three groups,theweight of tumor in LGP+DDP group was the lowest(P<0.01),and the lighter group was DDP group.The AI inexperimental group was higher than that in model group,and the AI in LGP+DDP group was the highest (P<0.01);theexpression of P-gp and Bcl-2 protein in LGP and LGP+DDP group was decreased (P<0.05),the expression of Baxprotein and the rate of Bax/Bcl-2 were increased(P<0.05);there was positive correlation between the expression ofP-gp and Bcl-2,as well as,negative correlation between the expression of P-gp and Bax (P<0.01).ConclusionLGPcould inhibit the growth of the transplanting tumor of murine cervical carcinoma U14,and modality therapy wasmore efficiency when combined with DDP;LGP can induce apoptosis by decreasing the expression of Bcl-2 protein andincreasing the expression of Bax protein,and enhance the chemotherapy sensitivity by decreasing the expression ofP-gp protein.