摘要
目的探讨缺氧诱导因子-1α(HIF-1α)在高压氧(HBO)调控宫颈癌细胞放射敏感性中的作用及其机制.方法细胞培养完成后将宫颈癌Hela细胞分为对照组、HBO组及HBO+HIF-1α组,采用CCK-8、克隆形成实验、流式细胞术及体内小鼠荷瘤实验检测Hela细胞增殖、克隆形成能力、凋亡及成瘤能力.结果与对照组(0 Gy)相比,2、4、6和8 Gy剂量的辐照均能抑制宫颈癌Hela细胞的增殖能力和克隆形成能力,并促进细胞凋亡(均P<0.05);相同辐照剂量2、4 Gy)下,HBO组细胞较对照组增殖和克隆形成能力明显降低、而凋亡水平明显升高(均P<0.05);与对照组相比,HBO组Hela细胞中HIF-1α的蛋白表达水平降低(P<0.05),与HBO组相比,HBO+HIF-1α过表达组Hela细胞的增殖能力提高,而凋亡水平受到明显抑制(均P<0.05);与对照组相比,HBO组生成的瘤体明显减小,但是HIF-1α过表达后该作用被抑制,且HBO组肿瘤组织中HIF-1α、Bcl-2的表达较对照组明显降低,而Bax和cleaved-caspase-3的表达升高,同样,此作用被HIF-1α过表达后抑制(均P<0.05).结论HBO能够通过下调HIF-1α的表达增强宫颈癌Hela细胞的放射敏感性.
Objective To explore the effect and mechanism of hypoxia inducible factor-1α(HIF-1α) on the enhanced radiosensitivity of cervical cancer cells by hyperbaric oxygen (HBO).Methods The cervical cancer Hela cells were divided into the control group,the HBO group and the HBO + HIF-1α group.CCK-8,clone formation assay,flow cytometry and tumor-loaded assay in mice were used to detect the proliferation of Hela cells,the capacity of clone formation,the apoptosis and tumorigenesis respectively.Results As compared with the control group (at the dosage of 0 Gy),the irradiation at the dosages of 2,4,6 and 8 Gy could inhibit the proliferation of Hela cells,the capacity of clone formation and the promotion of apoptosis (all P < 0.05).At the same irradiation levels (2,4 Gy),the proliferation and the capacity of clone formation of the HBO group all decreased significantly,as compared with those of the control group,while apoptosis obviously increased (all P < 0.05).As compared with the control group,the protein expression level of Hela cells in the HBO group decreased (P < 0.05).As compared with the HBO group,the proliferation of Hela cells in the HIF-1α over-expression group increased,while apoptosis level was significantly inhibited (all P < 0.05).As compared with the control group,the tumor size of the HBO group obviously reduced.However,its capacity was inhibited with the over-expression of HIF-1α.Furthermore,the expression levels of HIF-1α and Bcl-2 decreased,as compared with those of the control group,while Bax and cleaved-caspase-3 expression levels increased.Similarly,this activity was inhibited with the over-expression of HIF-1α(all P < 0.05).Conclusion This study has demonstrated that HBO could enhance the radiosensitivity of cervical cancer cells through down-regulation of HIF-1α.
作者
张冬雅
郭红军
冯巍
Zhang Dongya;Guo Hongjun;Feng Wei(Department of Gynecology ,First Affiliated Hospital of Zhengzhou Univiersity, Zhengzhou 450052, China)
出处
《中华航海医学与高气压医学杂志》
CAS
CSCD
2019年第4期315-319,共5页
Chinese Journal of Nautical Medicine and Hyperbaric Medicine
