血管生成抑制剂联合分化诱导剂治疗结肠癌的实验研究

Experimental study on angiogenesis inhibitor combined with differentiation inducer in the treatment of colon cancer in mice

目的通过建立人LOVO细胞结肠癌裸鼠皮下移植瘤模型,研究血管生成抑制剂(TNP-470)联合分化诱导剂(RA)抗结肠癌生长的效应,二者是否具有协同效果。方法建立人LOVO细胞结肠癌裸鼠皮下移植瘤模型,模型建立后分组治疗,按治疗方式分为对照组、TNP-470组、RA组和联合组(TNP-470+RA)至治疗结束时处死裸鼠,测量皮下移植瘤重量,计算抑瘤率;检测肿瘤组织结肠癌细胞凋亡指数(AI)。结果裸鼠皮下移植瘤瘤重、抑瘤率,联合组和对照组及TNP-470组、RA组比较差异均有统计学意义(P<0.05),且TNP-470组、RA组和对照组之间差异亦有统计学意义(P<0.05)。治疗组与对照组癌细胞AI比较,差异有统计学意义(P<0.05);且联合组与RA组和TNP-470组癌细胞的AI比较,差异也有统计学意义(P<0.05)。结论血管生成抑制剂TNP-470与分化诱导剂RA联合治疗结肠癌裸鼠皮下移植瘤比TNP-470或RA单药治疗具有更强的抑瘤作用,TNP-470通过抑制肿瘤血管生成,切断肿瘤细胞的血供和营养供给,抑制结肠癌裸鼠皮下移植瘤的生长;而RA通过诱导肿瘤细胞凋亡,降低VEGF的表达抑制肿瘤的生长,二者联和应用,抗肿瘤效应明显增强。

Objective To investigate the anti-cancer growth and inhibition metastasis effects of angiogenesis inhibitor （TNP-470） combination with differentiation inducer （RA） by human colon cancer xenografts into nude mice.Methods The transplanted tumor models were established by implanting colon cancer LOVO cell into nude mice. The nude mice were randomly divided into 4 groups.The treatment began respectively from one day after implantation to tumor metastased,and all the nude mice were sacrificed at the end of treatment. The inhibition effect on tumor growth was observed by weighing the tumor and detecting apoptosis index （AI） of xenografts tissue.Results There was a significant difference in the weight of implanted tumors among the four groups （P〈0.05）,and between TNP-470 group as well as RA group and control group （P〈0.05）. TNP-470 and RA had an additive effect on tumor inhibition,and the AI in treatment groups was significantly increased （P〈0.05）,and there was a significant difference in AI between RA group and TNP-470 group （P〈0.05）. The typical morphological changes of apoptotic LOVO cells in combination group were observed.Conclusion The angiogenesis inhibitor TNP-470 combined with different inducer RA may have an additive effect on the growth of human colon cancer xenografts,and TNP-470 can inhibit growth of xenografts of human colon cancer in nude mice by inhibiting the expression of MVD of tumor tissue,and RA also can inhibit cancer cell proliferation by inducing apoptosis of colon cancer cell,inhibiting the expression of VEGF,therefore,which is a safe and effective anti-tumor strategy.