HA14-1对环磷酰胺治疗小鼠Lewis肺癌增敏作用的实验研究

HA14-1 Sensitizes Chemotherapy of Murine Lewis Lung Carcinoma to Cyclophosphamide

目的观察HA14-1对环磷酰胺(CTX)治疗Lewis肺癌小鼠的化疗增效作用,探讨其可能的作用机制。方法建立Lewis肺癌小鼠肿瘤模型,将40只C57BL/6小鼠随机分为4组:生理盐水组、CTX组、HA14-1组和CTX+HA14-1组,给药7d。于肿瘤接种22d处死小鼠,描绘各组肿瘤体积增长曲线、计算抑瘤率,免疫组织化学方法测定治疗前后Lewis肺癌细胞Bcl-2、Bax和Caspase-9蛋白的表达情况。结果HA14-1组与生理盐水组比较无明显抑制肿瘤体积的作用,CTX组、HA14-1组和CTX+HA14-1组的肿瘤体积较生理盐水组增长慢。HA14-1组的抑瘤率与生理盐水组比较无明显增加(P>0.05);CTX+HA14-1组及CTX组与生理盐水组比较,CTX+HA14-1组与CTX组比较,抑瘤率均明显增加(P<0.05)。CTX组、HA14-1组和CTX+HA14-1组Bcl-2蛋白表达均减少,且CTX+HA14-1组较CTX组Bcl-2蛋白明显减少(P<0.05)。CTX组、HA14-1组和CTX+HA14-1组Bax、Caspase-9蛋白表达增加,与生理盐水组比较差异有统计学意义(P<0.05);CTX+HA14-1组比CTX组Bax、Caspase-9蛋白表达明显增加(P<0.05)。结论HA14–1可以增加CTX的化疗作用,其作用机制可能是通过抑制Bcl-2蛋白的表达,增加Bax、Caspase-9蛋白表达,从而促使肿瘤细胞凋亡。

Objective To observe HA14-1 sensitizes Lewis lung carcinoma in mice to cyclophosphamide （CTX） and to explore its possible mechanism. Methods Forty Lewis lung carcinoma model mice were randomly divided into 4 groups： normal saline group,CTX group, HA14-1 group,CTX＋HA14-1 group. After the treatment of 7 days,all of the mice were killed on the 22nd day of tumor inoculation. The tumor volume growth curve of each group was described;tumor inhibition rate was caculatued;Bcl-2, Bax, Caspase-9 protein expression levels before and after the treatment were determined by immunohistochemistry. Results Compared to the normal saline group,HA14-1 group had no significant effect on inhibiting tumor volume,and the tumor volume in HA14-1 group increased less slowly than that of CTX group,HA14- 1 group and CTX＋HA14-1 group. Compared to the normal saline group,the tumor inhibition rate of HA14-1 group had no significant increase （P〉 0.05）,while that of CTX group and CTX ＋ HA14-1 group increased significantly （P〈 0.05）;compared to the CIX group,the tumor inhibition rate of CTX ＋ HA14-1 group increased significantly （P 〈 0.05）. Bcl-2 protein expression levels in CTX group,HA14-1 group and CTX＋HA14-1 group were lower than that in the normal saline group;compared to CTX group,Bcl-2 protein expression of CTX ＋ HA14-1 group reduced significantly. Compared to the normal saline group,the expression levels of Bax and Caspase-9 protein in CTX group, HA14-1 group and CTX＋HA14-1 group increased significantly （P〈 0.05）;compared to CTX group,CTX ＋ HA14-1 group increased more significantly （ P 〈 0.05 ）. Conclusion HA 14-1 might enhance the efficiency of CTX chemotherapy via inhibiting the expression of Bcl-2, increasing the expression of Bax and caspase-9 and promoting tumor cell apoptosis.