白藜芦醇抑制人结肠癌细胞增殖的作用与促进骨形态蛋白9及其受体表达的关系研究  

Study on relationship between anti-proliferation effect of resveratrol and resveratrol-induced bone morphogenetic protein 9 and its receptors in colon cancer cells

作　　者：曾于桦 邵英[1,2] 李洋[1,2] 陈前昭 任文艳[1,2] 周林云[1,2] 周益[1,2] 刘荣兴[1,2] 何百成[1,2] 

机构地区：[1]重庆市生物化学与分子药理学重点实验室 [2]重庆医科大学药理教研室,重庆400016

出　　处：《中国药理学通报》2016年第12期1705-1711,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81572226)

摘　　要：目的研究白藜芦醇(resveratrol,Res)对人结肠癌LoVo细胞增殖的抑制作用与骨形态蛋白9(bone morphorgenetic protein 9,BMP9)之间的可能关系。方法采用结晶紫染色与流式细胞术检测Res对Lo Vo细胞增殖的抑制作用;流式细胞术检测Res对Lo Vo细胞凋亡的诱导作用。利用RTPCR和Western blot检测Res在Lo Vo细胞中对BMP9表达的影响,以及对BMP9的受体ALK2和ALK3表达的影响。采用ALK2和ALK3的抑制剂,通过结晶紫染色分析BMP9介导Res抑制Lo Vo细胞增殖的可能机制。结果与对照组相比,Res明显呈浓度依赖性抑制Lo Vo细胞增殖,并诱导Lo Vo细胞发生S期阻滞;Res呈浓度依赖性增加Lo Vo细胞凋亡比例;Res促进BMP9的mRNA表达并明显增加其蛋白水平;外源性过表达BMP9能增强Res对Lo Vo细胞的增殖抑制和诱导凋亡作用;Res能诱导BMP9的受体ALK2和ALK3的mRNA表达,抑制ALK2和ALK3能明显促进Lo Vo细胞增殖,并减弱Res对Lo Vo细胞增殖的抑制作用。结论Res对Lo Vo细胞的增殖具有明显抑制作用,这种作用可能与Res促进BMP9及其受体表达有关。Aim To study the anti-proliferation effect of resveratrol（ Res） and the role of Res-induced bone morphorgenetic protein 9（ BMP9） in this process in colon cancer cells. Methods Crystal violet staining and flow cytomtry were introduced to assay the antiproliferation effect of Res in LoVo cells. The effect of Res on apoptosis in LoVo cells was also detected with flow cytometry. Then,RT-PCR and Western blot assaywere employed to unveil the effect of Res on the expression of BMP9. The effect of BMP9 on the anti-proliferation of Res in LoVo cells was analyzed with crystal violet staining and flow cytometry too. Finally, the effect of Res on the expression of ALK2 and ALK3 was assayed with RT-PCR,and the inhibitor of ALK2 and ALK3 was used to figure out the possible mechanism of BMP9 on Res-induced proliferation inhibition in LoVocells. Results Res apparently inhibited the proliferation,arrested the cell cycle at S phase in LoVo and increased the percentage of apopotic cells in LoVo cells.Res increased the expression of mRNA and protein of BMP9 concentration dependently. Exogenous expressed-BMP9 enhanced the anti-proliferation and apoptosis inducing effects of Res in LoVo cells, but BMP9 knockdown decreased these effects of Res. Although Res had no apparent effect on increasing thephosphorylation of Smad1 /5 /8,it increased the expression of ALK2 and ALK3. Inhibition of ALK2 and ALK3 decreased the anti-proliferation effect of Res partly in LoVo cells. Conclusion Res is potent to inhibit the proliferation of LoVo cells,Which may be mediated by up-regulating the expression of BMP9 and its receptor at least.

关 键 词：白藜芦醇 骨形态蛋白9 结肠癌 LOVO细胞 增殖抑制 

分 类 号：R282.71[医药卫生—中药学] R329.24[医药卫生—中医学]