[1]刘海琴,沈冬祎,吕嘉婧,等.从Cyclin E1-CDK2-CKIs通路探讨芪灵扶正清解方抑制肝癌细胞株Hep1-6增殖的作用机制[J].福建医药杂志,2022,44(01):111-114.
 LIU Haiqin,SHEN Dongyi,LV Jiajing,et al.Qiling Fuzheng Qingjie decoction inhibit the proliferation of hepatoma cell line Hep1-6 via Cyclin E1-CDK2-CKIs signaling pathway[J].FUJIAN MEDICAL JOURNAL,2022,44(01):111-114.
点击复制

从Cyclin E1-CDK2-CKIs通路探讨芪灵扶正清解方抑制肝癌细胞株Hep1-6增殖的作用机制()
分享到:

《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
44
期数:
2022年01期
页码:
111-114
栏目:
基础研究
出版日期:
2022-02-15

文章信息/Info

Title:
Qiling Fuzheng Qingjie decoction inhibit the proliferation of hepatoma cell line Hep1-6 via Cyclin E1-CDK2-CKIs signaling pathway
文章编号:
1002-2600(2022)01-0111-04
作者:
刘海琴沈冬祎1吕嘉婧2罗秀2陈旭征林久茂章尤权3
福建中医药大学中西医结合研究院福建省中西医结合老年性疾病重点实验室(福州350122)
Author(s):
LIU Haiqin SHEN Dongyi LV Jiajing LUO Xiu CHEN Xuzheng LIN J iumao ZHANG Youquan
Fujian Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine geriatric Diseases, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
关键词:
芪灵扶正清解方 Hep1-6细胞 细胞周期 CDK2 CKIs
Keywords:
Qi Ling Fuzheng Qingjie decoction Hep1-6 cells cell cycle CDK2 CKIs
分类号:
R73-3
文献标志码:
A
摘要:
目的 从周期蛋白Cyclin E1-细胞周期依赖性蛋白激酶2(CDK2)-CDKs抑制因子CKIs (Cyclin E1-CDK2-CKIs)信号通路角度探讨芪灵扶正清解方(QL)调控小鼠肝癌Hep1-6 细胞株增殖的机制。方法 体外培养Hep1-6细胞,分别给予不同剂量的QL醇提物(0、31.25、62.5、125、250、500、1000 ug/mL)干预Hep1-6细胞株24h、48h和72h。MTT法检测细胞活力;流式细胞术检测细胞周期各个时相的比例;Westernblot检测CDK2、周期蛋白CyclinE1、视网膜母细胞瘤Rb、磷酸化Rb(p-Rb)以及CDKs抑制因子(CKIs) p57KIP2和p27KIP1的蛋白水平。结果 QL醇提物能显著抑制Hepl-6细胞的生长活力,呈剂量依赖性; Hep1-6细胞周期被阻滞在G0/G1期,S期的DNA合成被抑制; QL醇提物下调了CDK2、Cyclin E1、p-Rb的蛋白水平,上调了p57KIP2和p27KIP1的蛋白水平。结论 QL方通过抑制CDK2与Cyclin E1的结合,同时正向调控CKIs抑制CyclinE1CDK2复合物的激酶活性,从两方面抑制下游Rb的磷酸化水平,进而有效抑制肝癌Hepl-6细胞的增殖。
Abstract:
Objective To investigate the effects of Qiling Fuzheng Qingjie decoction (QL) on the proliferation of hepatoma cell line Hep1-6 via Cyclin E1-CDK2-CKIs signaling pathway. Methods Hep1-6 cells were cultured in vitro and treated with different doses of QL ethanol extract (0, 31.25, 62.5, 125, 250, 500, 1000 pg/mL) for 24 h, 48 h and 72 h, Cell viability was detected by MTT method; Flow cytometry was used to detect the ratio of each phase of the cell cycle; W estern blot was used to detect cycle-dependent protein kinases CDK2,Cyclin E1,retinoblastoma Rb, phosphorylated Rb (p-Rb) and CDKs inhibitor (CKIs) p57KIP2 and p27KIP1. Results QL ethanol extract could significantly inhibit the growth activity of Hep1-6 cells in a dose-dependent manner. Cell cycle was blocked in G0/G1 phase, and DNA synthesis in S phase was inhibited. The QL ethanol extract down regulated the protein levels of CDK2,Cyclin E1 and p-Rb,and up-regulated the protein levels of p57KIP2 and p27KIP1. Conclusion QL decoction could inhibit the proliferation of hepatoma Hep1-6 cells by inhibiting the binding of CDK2 and Cyclin E1 and positively regulating CKIs to inhibit the kinase activity of Cyclin E1-CDK2 complex, then inhibiting the phosphorylation of Rb.

参考文献/References:

[1] Sung H,Ferlay J,Siegel R L,et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality World-wide for 36 Cancers in 185Countries [J]. CA CancerJ Clin,2021,71 (3): 209-249.
[2] 蔡立业.扶正清解方加减对气阴两虚型胃癌根治术后化疗的临床疗效观察[D].福建:福建中医药大学,2013.
[3] 陈立武,郑春松,杜建.用分子对接法探讨清热消癥饮的抑瘤作用机制[J].中国临床药理学与治疗学,2007,12 (3):324-328.
[4] ChenXZ, CaoZ Y, Zhang Y Q, et al. Fuzheng Qingjie granules inhibit growth of hepatoma cells via inducing mitochondria- mediated apoptosis and enbancing immune function [J]. Integr Cancer Ther,2017,16 (3): 329-338.
[5] ChenXZ, LiJ N, Zhang Y Q, et al. Fuzheng Qingjie recipe induces apoptosis in HepG2 cells via P38 MAPK activation and the mitochondria- dependent apoptotic pathway [J]. Mol Med Rep,2014,9 (6): 2381-2387.
[6] Kawabe T. G2 checkpoint abrogators as anticancer drugs [J]. Mol Cancer Ther,2004,3 (4): 513-519.
[7] Lim s, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation [J]. Development, 2013, 140 (15): 3079-3093.
[8] Stefanikovd A, KlacanovaK, Pilchovd I, et al. Cyeli-dependent kinase2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737 [J]. Gen Physiol Biophys,2017,36 (5): 539-547.
[9] Tang J, Wang F, Cheng G,et al. Wilms' tumor 1-associating protein promotes renal cell carcinoma proliferation by regulating CDK2 mRNA stability [J]. J Exp Clin Cancer Res,2018,37 (1): 40.

更新日期/Last Update: 2022-02-15