Stathmin siRNA抑制人胃癌SGC-7901细胞裸鼠移植瘤的生长并诱导细胞凋亡

Stathmin siRNA induces growth inhibition and apoptosis of human gastric carcinoma SGC-7901 cell xenografts in nude mice

目的:探讨微管解聚蛋白stathmin对人胃癌SGC-7901细胞裸鼠移植瘤的生长和细胞凋亡的影响及其可能的分子机制。方法:将0.1 mL SGC-7901细胞悬液(5×1010/L)接种于裸鼠背部一侧皮下,建立人胃癌SGC-7901细胞裸鼠移植瘤模型,将其分为3组:PBS组(PBS治疗)、对照siRNA组(接种对照siRNA,终浓度为100 nmol/L)和stathmin siRNA组(接种stathmin siRNA,终浓度为100 nmol/L),治疗方式均为腹腔注射。连续2周观察荷瘤裸鼠的生长情况,免疫组织化学方法检测增殖抗原Ki-67的表达,采用TUNEL研究肿瘤组织中细胞的凋亡,Western blotting检测裸鼠肿瘤组织中stathmin、Bcl-2和Bax蛋白的表达。结果:Stathmin siRNA能明显抑制胃癌裸鼠移植瘤的生长(P<0.05),stathmin siRNA组中裸鼠移植瘤的重量明显低于PBS组和对照siRNA组(P<0.05)。免疫组化结果表明,stathmin siRNA组中Ki-67的增殖指数明显低于PBS组和对照siRNA组(P<0.05)。TUNEL结果显示,stathmin siRNA组的凋亡细胞数显著高于PBS组和对照siRNA组(P<0.05)。Western blotting结果表明,与PBS组和对照siRNA组相比,stathmin siRNA组中stathmin和Bcl-2蛋白的表达显著下调,而Bax蛋白表达明显上升(均P<0.05)。结论:Stathmin在胃癌细胞增殖和细胞凋亡的调控中发挥重要作用,本研究有望为胃癌分子靶向治疗提供理论依据。

AIM： To investigate the effects of microtubule -destabilizing protein stathmin on the growth and apeptosis of human gastric carcinoma SGC ,7901 cell xenografts in nude mice. METHODS： The model of xenograft was established by implanting 0. 1 mL gastric carcinoma SGC -7901 cell suspension （5 × 10^10/L） into the nude mice. The model animals were randomly divided into 3 groups including PBS group （ treated with PBS）, control siRNA group （ treated with control siRNA at the final concentration of 100 nmol/L） and stathmin siRNA group （ treated with stathmin siRNA at the fmal concentration of 100 nmol/L） by intraperitoneal injection. The status of xenografted nude mice was observed for continuous 2 weeks. Subsequently, the expression of proliferative antigen Ki - 67 was detected by immunohistochemistry, and TUNEL was utilized to analyze cell apeptosis. The protein expression of stathmln, Bcl - 2 and Bax was determined by Western blotting in the tumor tissue of xenografted nude mice. RESULTS： siRNA targeting stathmin obviously inhibited the growth of nude mouse xenografts （P 〈 0.05 ）, and the weight of nude mouse xenografts in stathmin siRRA group was significantly lower than that in PBS group and control siRNA group. Additionally, the proliferation index of Ki - 67 in stath- rain siRNA group was markedly lower than that in PBS group and control siRNA group. The number of apeptofic cells in stathmin siRNA group was evidently higher than that in PBS group and control siRNA group. Furthermore, the protein ex- pression levels of stathmin and Bcl - 2 in stathmln siRNA group were obviously down - regulated, and the expression of Bax protein was significantly increased compared with PBS group and control siRNA group. CONCLUSION： Stathndn may play an important role in cell proliferation and apoptosis in gastric carcinoma, indicating a molecular target for treating gas- tric carcinoma.