Zhong Zhiwei, Dong Zhuo, Yang Lihua, Chen Xiaoqiang, Gong Zhaohui
Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo 315211;
Exp Ther Med. 2012 Aug;4(2):267-272. doi: 10.3892/etm.2012.580. Epub 2012 May 17.
Green tea catechins are known to function as anticancer agents via inhibition of carcinogenesis during the initiation, promotion and progression stages. Many potential mechanisms have been proposed, yet the precise mechanism of lung cancer prevention by green tea catechins remains unclear. microRNAs (miRs) are a class of 21-24 nucleotide small non-coding RNAs and play critical roles throughout cellular development and regulation. Emerging evidence demonstrates that tea catechins influence the expression of miRs in human cancer cells to inhibit tumorigenesis. Both let-7a-1 and let-7g were detected in the human lung cancer cells treated with tea catechins. The cell viability and cell cycle were analyzed after tea catechins treatment. In the present study, we found that tea catechins upregulated the tumor-suppressor miRs, let-7a-1 and let-7g, in lung cancer cell lines. The upregulation of let-7a/7g repressed the expression of their targets, C-MYC and the regulatory protein of LIN-28, at the mRNA and protein levels. Moreover, the cell growth assay indicated that tea catechins significantly inhibited cell proliferation, and the flow cytometric analysis revealed an increase in the number of cells in the G2/M phase and a decrease in the number of cells in the S phase after treatment with tea catechins. These observations suggest that green tea catechins mediate the inhibition of proliferation of lung cancer cells through the let-7 signaling pathway.
已知绿茶儿茶素可在致癌作用的起始、促进和进展阶段通过抑制致癌过程发挥抗癌作用。虽然已经提出了许多潜在机制,但绿茶儿茶素预防肺癌的确切机制仍不清楚。微小RNA(miRs)是一类由21 - 24个核苷酸组成的小非编码RNA,在整个细胞发育和调控过程中发挥关键作用。新出现的证据表明,茶儿茶素会影响人类癌细胞中miRs的表达以抑制肿瘤发生。在用茶儿茶素处理的人类肺癌细胞中检测到了let - 7a - 1和let - 7g。在茶儿茶素处理后分析了细胞活力和细胞周期。在本研究中,我们发现茶儿茶素上调了肺癌细胞系中肿瘤抑制性miRs,即let - 7a - 1和let - 7g。let - 7a/7g的上调在mRNA和蛋白质水平上抑制了它们的靶标C - MYC和LIN - 28调节蛋白的表达。此外,细胞生长试验表明茶儿茶素显著抑制细胞增殖,流式细胞术分析显示,用茶儿茶素处理后,G2/M期细胞数量增加,S期细胞数量减少。这些观察结果表明,绿茶儿茶素通过let - 7信号通路介导肺癌细胞增殖的抑制。