生长抑素类似物通过细胞生长抑制和细胞溶解途径以SSTR2依赖的方式抑制癌细胞增殖  

Somatostatin analogs inhibited cancer cell proliferation in a SSTR2-dependent manner via both cytostatic and cytotoxic pathways

作　　者：邹奕[1] 肖小平[1] 李月琴[1] 张欣[1] 周天鸿[1] 

机构地区：[1]暨南大学生物工程学系,广东广州510632

出　　处：《暨南大学学报（自然科学与医学版）》2009年第3期325-330,共6页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：教育部科学技术研究重点项目(207144);暨南大学引进优秀人才科研启动项目(51207016)

摘　　要：通过在两个具有不同内源性生长抑素受体(SSTR)表达谱的癌细胞系capan-2和A549中过表达SSTR2,用生长抑素类似物(SSA)奥曲肽或者伐普肽(RC-160)处理实验组的癌细胞,对过表达SSTR2和生长抑素类似物的抗肿瘤增殖效果通过细胞增殖实验进行了研究,而且进一步通过免疫印记的方法研究了SSA/SSTR2涉及的信号通路.结果表明,过表达SSTR2明显抑制了内源性SSTR2表达阳性和阴性癌细胞增殖,而单独使用奥曲肽或者伐普肽对癌细胞增殖影响甚微.然而,在过表达SSTR2的癌细胞中奥曲肽或者伐普肽则可明显抑制癌细胞的增殖,而且具有剂量依赖性.深入研究发现SSA/SSTR2是通过细胞周期阻滞和促凋亡来抑制细胞增殖.结果提示SSTR2可作为候选基因用于本身SSTR2表达阳性或阴性肿瘤的基因治疗,细胞内SSTR2的水平可能是影响肿瘤进程和SSA治疗效果的一个关键因素.Exogenous human SSTR2 was overexpressed in two cancer cell lines, capan-2 ceils and A549 cells, which have different expression profiles of endogenous SSTRs. The experimental cancer cells were treated with octreotide or RC-160 at different concentrations. The anti-tumor effects of SSTR2 over- expression and the treatment of octreotide/RC-160 were studied by cell proliferation assessment. The potential pathways involved in SST/SSTR2 signaling were investigated using immunoassays. The results presented in this study showed that overexpression of SSTR2 dramatically inhibited the proliferation of both SSTR2-positive and SSTR2-negative cancer cells. Application of octreotide/RC-160 alone resulted in minimal impact on cancer ceil proliferation. However, Octreotide/RC-160 significantly inhibited the proliferation of cancer ceils overexpressing SSTR2 in a dose-dependent fashion. Further investigations demonstrated that SSA/SSTR2 inhibited proliferation via both cell cycle arresting and promoting apoptosis. It suggested that SSTR2 could be a promising candidate for gene therapy for both SSTR2-positive and SSTR2-negative tumors. The cellular level of SSTR2 might be a critical factor that affects both tumor progression and the outcomes of somatostatin analogue treatment.

关 键 词：生长抑素 受体 激酶 奥曲肽 伐普肽 

分 类 号：R394.3[医药卫生—医学遗传学]