ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins
ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins
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DOI：
10.1007/s12032-015-0490-5
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发表时间：
2015-03-01
期刊：
影响因子：
3.4
通讯作者：
Xu, Juan
中科院分区：
文献类型：
--
作者：
Bai, Lixia;Mao, Rui;Xu, Juan
针对MAPK的小分子抑制剂作为一种生物学上可行的模型已被广泛应用于某些癌症的治疗，但尚未有人将其用于宫颈癌的治疗。ERK 1/2是MAPK激酶之一，在宫颈癌组织中高表达。本研究旨在探讨ERK 1/2抑制剂U 0126对宫颈癌细胞增殖和凋亡的影响及其相关机制。本研究采用CCK-8法和细胞计数法检测ERK 1/2抑制剂U 0126对宫颈癌Hela细胞和C33 A细胞增殖的影响。流式细胞仪检测细胞周期和凋亡。Western blot检测ERK 1/2、c-Fos和c-Jun蛋白表达水平。结果表明，ERK 1/2抑制剂U 0126下调ERK 1/2蛋白后，Hela和C33 A细胞增殖受到抑制，细胞凋亡受到促进，细胞周期中G 0/G1期比例增加，G2/M期比例减少。下调Hela和C33 A细胞ERK 1/2蛋白后，p-c-Fos蛋白表达水平下降，p-c-Jun蛋白表达水平升高。本研究结果提示ERK 1/2可能促进宫颈癌细胞的发展，提示ERK 1/2抑制剂可能作为宫颈癌治疗的有效靶点而发挥作用。其可能通过调控c-Fos和c-Jun转录因子的表达而抑制宫颈癌细胞的生长。
Small-molecule inhibitors targeted MAPK have been wildly used for some cancer therapeutics as a biologically viable model, but no one has been used for cervical caner. ERK1/2, one of MAPK kinases, is expressed high in cervical cancer tissue. The aim of the present study was to evaluate the effects of ERK1/2 inhibitor U0126 on proliferation and apoptosis of cervical cancer cells and appraise the correlated mechanism of the effects. In this study, the cell proliferation of Hela and C33A cervical cancer cells was tested by Cell Counting Kit-8 (CCK8) assay and cell counting after treated with ERK1/2 inhibitor U0126. The cell cycle and apoptosis were evaluated by flow cytometry (FCM). The protein levels of ERK1/2 and c-Fos and c-Jun were detected by Western blot. The results indicated that after down-regulating ERK1/2 proteins with the inhibitor U0126, Hela and C33A cells proliferation was inhibited, cell apoptosis was promoted, the proportions of G0/G1 stage in cell cycle increased, and G2/M stages decreased. After down-regulating ERK1/2 proteins of Hela and C33A cells, the expression levels of p-c-Fos protein decreased, while p-c-Jun protein increased. The results of this study indicated that ERK1/2 may promote the development of cervical cancer cells, suggesting ERK1/2 inhibitor may be used as an effective target for cervical cancer therapies working for. It might inhibit cervical cancer cells growth via regulating the transcription factors expression of c-Fos and c-Jun.