丹参酮ⅡA对人结肠癌HT29细胞TGF-β1、Bcl-2表达和细胞生长的影响

Effects of Tanshinone ⅡA on human colon cancer cell growth and expressions of TGF-β1 and Bcl-2

目的观察丹参酮ⅡA对人结肠癌细胞HT29生长及其对转化生长因子β1(TGF-β1)、B细胞淋巴瘤-2(Bcl-2)基因表达的影响,为结肠癌治疗提供理论基础。方法分别采用不同浓度的丹参酮ⅡA处理人结肠癌HT29细胞,MTT法检测细胞生长情况;实时荧光定量PCR(Real-time PCR)检测不同处理组所收集细胞TGF-β1和Bcl-2mRNA表达;小鼠腋下接种HT29细胞制备小鼠结肠癌移植瘤模型,随机分为对照组和丹参酮ⅡA处理组,每周测量肿瘤体积1次,4周后摘取肿瘤称重并保存肿瘤;Western blot检测提取自HT29细胞和肿瘤组织内TGF-β1、Bcl-2蛋白表达。结果随着丹参酮ⅡA浓度升高,HT29生长抑制率增加;丹参酮ⅡA浓度增加对TGF-β1和Bcl-2mRNA及蛋白表达产生抑制作用;丹参酮ⅡA对小鼠结肠癌移植瘤的体积抑制率为28.63%;Westernblot结果表明,与对照组比较,丹参酮ⅡA组肿瘤体积内TGF-β1、Bcl-2蛋白水平降低。结论丹参酮ⅡA对结肠癌细胞HT29及其裸鼠模型移植瘤的生长具有明显的抑制作用,其机制可能与丹参酮ⅡA下调TGF-β1和Bcl-2表达有关。

Objective To observe the effects of Tanshinone ⅡA on the growth of HT29 and the expressions of TGF-β1 and Bcl-2 in colon cancer so as to provide theoretical assistance for treatment of colon cancer. Methods Human colon cancer HT29 cells were cultured for different time after treated with various concentrations of Tanshinone ⅡA,respectively. MTT method was used to detect cell growth. The human colon cancer tumors on nude mice were randomly divided into control group and Tanshinone ⅡA treatment group,and the tumor volume was measured once a week. After 4 weeks,the tumors were preserved. The levels of TGF-β1 and Bcl-2 protein in the HT29 cells and tumor tissues were detected by Western blot. Results With the increase of Tanshinone ⅡA concentration,the growth inhibition rate of HT29 increased;Tanshinone ⅡA downregulated the mRNA and protein levels of TGF-β1 and Bcl-2 gene in HT29. The volume inhibition rate of Tanshinone ⅡA on mouse colon cancer transplanted tumor was 28.63%. The results of Western blot showed that the levels of TGF-β1 and Bcl-2 protein were decreased in Tanshinone ⅡA group compared with control group. Conclusion Tanshinone ⅡA has significant inhibitory effects on the growth of colon cancer cell HT29 and its xenografts model. This mechanism may be realized by the downregulation of TGF-β1 and Bcl-2 expressions via Tanshinone ⅡA.