法尼基转移酶抑制剂和香叶基香叶基转移酶抑制剂对皮肤角质形成细胞增殖的抑制作用  

Inhibition of keratinocyte proliferation by FTI and GGTI

作　　者：周宏 李名聪 顾亚男 朱婷婷 罗欣[1] 张胜权[1] Zhou Hong;Li Mingcong;Gu Yanan(Dept of Biochemistry and Molecular, Anhui Medical University, Hefei 230032)

机构地区：[1]安徽医科大学生物化学与分子生物学教研室,合肥230032

出　　处：《安徽医科大学学报》2020年第2期155-158,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81271748);安徽省高等学校自然科学研究项目(编号:KJ2017A195)。

摘　　要：目的探讨法尼基转移酶抑制剂(FTI)和香叶基香叶基转移酶抑制剂(GGTI)对皮肤角质形成细胞(KCs)增殖的影响。方法使用不同浓度的FTI、GGTI对KCs进行处理,细胞活力测定实验(MTS)法分析KCs增殖受各处理组的影响;利用流式细胞术检测各加药组细胞周期受一定浓度FTI、GGTI的影响;Western blot分析各加药组细胞周期蛋白CyclinB1、CyclinE和P21及pAKT和pERK1/2表达量受一定浓度FTI、GGTI的影响。结果MTS显示FTI、GGTI对KCs增殖有抑制作用,并呈浓度依赖性,FTI(5μmol/L)、GGTI(5μmol/L)时KCs细胞活力最小,抑制率分别为14.7%、24.5%。流式周期结果表示FTI、GGTI阻滞KCs在G1、G2、S各期不明显。Western blot结果表明FTI、GGTI均能够下调CyclinB1,并且可以上调P21和CyclinE的表达。同时,FTI、GGTI能促进P13K-AKT信号通路的激活,抑制MAPKS-ERK1/2信号通路的激活。结论FTI、GGTI对原代KCs的增殖有抑制作用。Objective To investigate the effects of farnesyltransferase inhibitor(FTI)and geranylgeranyl transferase inhibitor(GGTI)on the proliferation of keratinocytes(KCs).Methods KCs were treated with different concentrations of FTI and GGTI.MTS analysis was used to analyze the effect of each treatment group on KCs cell proliferation.Flow cytometry was used to detect the effect of certain concentrations of FTI and GGTI on the cell cycle.Western blot was used to analyze the effects of certain concentrations of FTI and GGTI on the expressions of CyclinB1,CyclinE and P21,pAKT and pERK1/2 in each group.Results MTS showed that FTI and GGTI inhibited the proliferation of KCs in a concentration-dependent manner.The activity of KCs was the smallest in FTI(5μmol/L)and GGTI(5μmol/L),and the inhibition rates were 14.7%and 24.5%,respectively.The results of the flow cycle indicated that the FTI and GGTI retardation of KCs were not obvious in all phases of G1,G2 and S.Western blot results showed that FTI and GGT could down-regulate CyclinB1 and up-regulate the expression of P21 and CyclinE.At the same time,FTI and GGTI could promote the activation of P13K-AKT signaling pathway and inhibit the activation of MAPKS-ERK1/2 signaling pathway.Conclusion FTI and GGTI have an inhibitory effect on the proliferation of primary KCs.

关 键 词：甲羟戊酸代谢途径 法尼基转移酶抑制剂 香叶基香叶基转移酶抑制剂 皮肤角质形成细胞 细胞增殖 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学]