过表达SSTR2通过多种信号途径抑制SSTR2表达阳性的肿瘤生长

Overexpression of SSTR2 inhibits growth of SSTR2-positive tumors via multiple signaling pathways

目的:研究转基因SSTR2对有不同内源性SSTRs表达谱的癌细胞增殖抑制及其潜在信号途径。方法:在裸鼠身上接种过表达SSTR2或LacZ的capan-2cell和A549细胞,观察肿瘤生长情况。在裸鼠身上构建capan-2移植瘤模型,通过皮下注射携带SSTR2基因的腺病毒,观察肿瘤生长情况。免疫印迹法分析可能涉及的信号途径。结果:过表达SSTR2能够抑制具有不同内源性SSTRs表达谱肿瘤的生长,包括capan-2具有内源性SSTR2表达。SSTR2过表达明显影响了凋亡途径、MAPK途径以及血管生成中的一些组件。结论:SSTR2有希望成为使用转基因治疗多数癌症的候选基因。

AIM： To study the anti - proliferation effect of overexpressed SSTR2 in experimental cancer with different profiles of endogenous SSTRs expressions and the possible signaling pathways involved. METHODS： In the first experiment, the growth of the tumor xenografts of the inoculated capan - 2 cells and A549 cells overexpressing SSTR2 or LacZ was investigated in nude mice. In the second experiment, the adenoviral vector expressing SSTR2 were introduced into experimental capan -2 xenografts by intratumoral injection. The growth inhibition of these experiment tumors was observed and the potential influences on different signaling pathways were analyzed by immunoassays. RESULTS： Overexpression of SSTR2 inhibited the growth of tumors with different profiles of endogenous SSTRs, including experimental capan - 2 xenografts that had endogenous SSTR2 expression. Overexpression significantly affected a number of components in apoptotic pathway, MAPK pathway and angiogenesis. CONCLUSION： SSTR2 is a promising candidate for gene therapy in a wide spectrum of cancers.