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  • 韦可璇,张华颖,林春香,宋秋露,赵伟.罂粟碱通过调节自噬对肝癌细胞放射敏感性的影响[J].广西科学,2023,30(3):614-623.    [点击复制]
  • WEI Kexuan,ZHANG Huaying,LIN Chunxiang,SONG Qiulu,ZHAO Wei.Effect of Papaverine on Radiosensitivity of Hepatocellular Carcinoma Cells by Regulating Autophagy[J].Guangxi Sciences,2023,30(3):614-623.   [点击复制]
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罂粟碱通过调节自噬对肝癌细胞放射敏感性的影响
韦可璇, 张华颖, 林春香, 宋秋露, 赵伟
0
(广西医科大学附属武鸣医院放疗科, 广西南宁 530199)
摘要:
为探究罂粟碱(Papaverine,PPV)和细胞自噬在原发性肝癌放射敏感性中的作用机理,将肝癌HepG2、Huh7细胞进行X射线照射,并将细胞分为阴性对照(NC)组、罂粟碱(PPV)组、单纯照射(IR)组,然后采用CCK8实验检测细胞的增殖情况,划痕实验检测细胞迁移情况,克隆形成实验检测细胞放射敏感性,实时定量PCR (RT-PCR)实验检测LC3B、ATG7 mRNA表达情况,蛋白免疫印迹(Western blot)实验检测自噬相关标志物LC3B、p62、p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR蛋白表达情况。研究结果显示,与NC组相比,罂粟碱对肝癌HepG2和Huh7细胞的增殖有明显的抑制作用(P<0.05),并可以抑制肝癌细胞的迁移能力(P<0.05),显著降低肝癌细胞LC3B、ATG7 mRNA的表达水平(P<0.05)和LC3-Ⅱ/LC3-Ⅰ的蛋白表达,提高p62、p-PI3K、p-AKT和p-mTOR的蛋白表达。此外,罂粟碱还可以提高肝癌细胞的放射治疗(RT)效果。上述结果表明罂粟碱通过PI3K/AKT/mTOR通路抑制HepG2、Huh7细胞自噬,从而抑制肝癌细胞的增殖和迁移能力,并提高肝癌细胞放射敏感性。
关键词:  罂粟碱  肝癌  自噬  放射敏感性  增殖  迁移
DOI:10.13656/j.cnki.gxkx.20230523.002
投稿时间:2022-09-16修订日期:2022-11-18
基金项目:广西自然科学基金项目(2017JJA10748),广西医疗卫生适宜技术开发与推广应用项目(S2018008),广西高校生物分子医学研究重点实验室开放课题项目(GXBMR201604),南宁市武鸣区科学研究与技术开发计划项目(20200213),广西壮族自治区卫生健康委员会西医类别自筹经费科研课题(Z20201311)和南宁市武鸣区重点研发计划项目(20210124)资助。
Effect of Papaverine on Radiosensitivity of Hepatocellular Carcinoma Cells by Regulating Autophagy
WEI Kexuan, ZHANG Huaying, LIN Chunxiang, SONG Qiulu, ZHAO Wei
(Department of Radiation Oncology, Wuming Hospital Affiliated of Guangxi Medical University, Nanning, Guangxi, 530199, China)
Abstract:
In order to explore the mechanism of Papaverine (PPV) and autophagy in the radio-sensitivity of primary hepatocellular carcinoma,HepG2 and Huh7 cells were irradiated by X-ray,and the cells were divided into Negative Control (NC) group,Papaverine (PPV) group and simple Irradiation (IR) group.The proliferation of cells was detected by CCK8 test,the migration of cells was detected by scratch test,the radio-sensitivity of cells was detected by clone formation test,and the expression of LC3B and ATG7 mRNA was detected by real-time quantitative PCR (RT-PCR).Western blot was used to detect the expression of autophagy-related markers LC3B,p62,p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR protein.The results showed that compared with NC group,papaverine could significantly inhibit the proliferation of hepatocellular carcinoma HepG2 and Huh7 cells (P<0.05).Papaverine could inhibit the migration ability of hepatocellular carcinoma cells (P<0.05).Papaverine could significantly decrease the expression of LC3B and ATG7 mRNA (P<0.05),decrease the protein expression of LC3-Ⅱ/LC3-Ⅰ and increase the protein expression of p62,p-PI3K,p-AKT and p-mTOR.In addition,papaverine can also improve the effect of radiotherapy on hepatocellular carcinoma cells.It is suggested that papaverine inhibits autophagy of HepG2 and Huh7 cells through PI3K/AKT/mTOR pathway,thereby inhibiting the proliferation and migration of liver cancer cells and improve the radio-sensitivity of liver cancer cells.
Key words:  papaverine  hepatocellular carcinoma  autophagy  radio-sensitivity  proliferation  migration

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