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目的探讨前胱天蛋白酶(procaspase)-3激活剂SM-1体内外对人胃癌BGC-823细胞的抗肿瘤作用及初步机制。方法体外MTT法测定SM-1对BGC-823细胞增殖的抑制作用,流式细胞仪分析不同浓度SM-1对BGC-823细胞凋亡率的影响,分别用Western印迹和RT-PCR测定SM-1对胱天蛋白酶(caspase)-3蛋白和procaspase-3mRNA表达的影响,采用裸鼠皮下移植瘤模型评价SM-1体内抗肿瘤作用。结果 SM-1体外呈剂量依赖性地抑制BGC-823细胞增殖并诱导其凋亡;SM-1暴露48 h后,caspase-3蛋白和procaspase-3 mRNA表达水平增加;在300 mg/kg剂量下,SM-1对BGC-823皮下移植瘤生长具有明显的抑制作用,其抑制率达到56.3%(P<0.05)。结论SM-1体内外对BGC-823细胞及皮下移植瘤具有较好的抑制作用,其机制主要通过激活procaspase-3诱导肿瘤细胞凋亡发挥抗肿瘤作用。
Objective To investigate the antitumor effect and mechanism of procaspase-3 activator SM-1 on human gastric cancer cell line BGC-823 in vitro and in vivo. Methods The inhibitory effect of SM-1 on proliferation of BGC-823 cells was determined by in vitro MTT assay. The effects of different concentrations of SM-1 on the apoptosis of BGC-823 cells were analyzed by flow cytometry. The expression of SM- 1 on caspase-3 protein and procaspase-3 mRNA expression in nude mice subcutaneously xenograft model evaluation SM-1 anti-tumor effect in vivo. Results SM-1 inhibited the proliferation and induced apoptosis of BGC-823 cells in a dose-dependent manner in vitro. The expression of caspase-3 protein and procaspase-3 mRNA increased after SM-1 exposure for 48 h. At the dose of 300 mg / kg SM-1 could inhibit the growth of BGC-823 subcutaneously and the inhibitory rate was 56.3% (P <0.05). Conclusion SM-1 can inhibit the growth of BGC-823 cells and subcutaneously xenografts in vitro and in vivo. The mechanism of SM-1 is to induce tumor cells apoptosis by activating procaspase-3.