|本期目录/Table of Contents|

Akt抑制剂MK-2206在缺氧环境下对结肠癌SW480细胞增殖、侵袭的影响

《现代肿瘤医学》[ISSN:1672-4992/CN:61-1415/R]

期数:
2022年12期
页码:
2135-2141
栏目:
论著（基础研究）
出版日期:
2022-05-12

文章信息/Info

Title:
The effects of Akt inhibitor MK-2206 on proliferation and invasion of colon cancer SW480 cells under hypoxia condition
作者:
刘 琦1; 郝朗松2; 何 奎2; 邓 洋2
1.湖北医药学院基础医学院，湖北 十堰 442000；2.贵州省人民医院，贵州 贵阳 550000
Author(s):
LIU Qi1; HAO Langsong2; HE Kui2; DENG Yang2
1.School of Basic Medical Sciences,Hubei University of Medicine,Hubei Shiyan 442000,China;2.Guizhou Provincial People's Hospital,Guizhou Guiyang 550000,China.
关键词:
转移性结直肠癌; 磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白; 缺氧诱导因子; 信号通路抑制剂
Keywords:
metastatic colorectal cancer; phosphatidylinositide 3-kinase/protein kinase B/mammalian target of rapamycin; hypoxia-inducible factor; signal pathway inhibitor
分类号:
R735.3+5
DOI:
10.3969/j.issn.1672-4992.2022.12.006
文献标识码:
A
摘要:
目的：探讨Akt抑制剂MK-2206在缺氧环境下对人结肠癌SW480细胞增殖、侵袭的影响。方法:根据CCK-8实验结果选择CoCl2和MK-2206的浓度，最后分成空白组、MK-2206组、CoCl2组、MK-2206+CoCl2组；Transwell小室实验检测四组细胞的迁移和侵袭能力；RT-PCR法检测各细胞组中Akt、mTOR、HIF-1α的mRNA表达水平；Western blot技术检测各细胞组中Akt、p-Akt、mTOR、p-mTOR、HIF-1α蛋白表达的差异性情况。结果:CoCl2诱导的缺氧环境可以促进SW480细胞的侵袭、迁移(P＜0.05)，同时能够促进HIF-1α的mRNA和蛋白表达(P＜0.05)，但是低浓度范围内的CoCl2对SW480细胞增殖活性无明显影响(P＞0.05)；MK-2206可以在体外的常氧和缺氧环境中抑制SW480细胞的增殖活性和侵袭、迁移能力(P＜0.05)；MK-2206能在体外的常氧环境下抑制SW480细胞的Akt、mTOR、HIF-1α的mRNA表达(P＜0.05)，缺氧环境无明显作用；同时MK-2206能够在常氧和缺氧环境中显著降低p-Akt、p-mTOR、HIF-1α的蛋白表达水平(P＜0.05)。 结论：Akt抑制剂MK-2206可以在体外的常氧和缺氧环境下抑制SW480细胞的增殖活性和侵袭能力，但缺氧环境可能会弱化MK-2206对SW480细胞迁移的抑制作用。
Abstract:
Objective:To investigate the effects of Akt inhibitor MK-2206 on the proliferation and invasion of human colon cancer SW480 cells under hypoxia condition.Methods:According to the results of CCK-8 experiment and the concentrations of CoCl2 and MK-2206,there were blank group,MK-2206 group,CoCl2 group and MK-2206+CoCl2 group.Transwell chamber test was used to detect the ability of cell migration and invasion,and RT-PCR technique was used to detect the mRNA expression of Akt,mTOR and HIF-1α in each cell group.Western blot was used to detect the difference of Akt,p-Akt,mTOR,p-mTOR and HIF-1α protein expression in different cell groups.Results:CoCl2-induced anoxic environment could not only promote the invasion and migration of SW480 cells (P＜0.05),but also promote the expression of mRNA and protein of HIF-1α (P＜0.05).However，CoCl2 at low concentration had no significant effect on the proliferation of SW480 cells (P＞0.05).MK-2206 can inhibit the proliferation,invasion and migration of SW480 cells in normoxic and hypoxic environment (P＜0.05).MK-2206 could inhibit the mRNA expression of Akt,mTOR and HIF-1α in SW480 cells under normoxic environment in vitro (P＜0.05),but had no effect in hypoxic environment.At the same time,MK-2206 could significantly reduce the protein expression levels of p-Akt,p-mTOR and HIF-1α in normoxic and hypoxic environment (P＜0.05).Conclusion:MK-2206 of Akt inhibitor can significantly inhibit the proliferation and invasion of SW480 cells under normoxic and hypoxic conditions in vitro.However,hypoxia may weaken the inhibitory effect of MK-2206 on the migration of SW480 cells.

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备注/Memo

备注/Memo:
贵州省卫生计生委科学技术基金(编号：gzwkj2018-1-034)
更新日期/Last Update: 1900-01-01