南蛇藤醇抑制宫颈癌细胞生物学行为的机制研究

doi:10.13418/j.issn.1001-165x.2020.04.011

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (4): 421-427.doi: 10.13418/j.issn.1001-165x.2020.04.011

南蛇藤醇抑制宫颈癌细胞生物学行为的机制研究

贾莹¹，　赵伟¹，　张欣媛²，　吴瑞³，　肖兵兵³

1.大庆龙南医院（齐齐哈尔医学院第五附属医院），黑龙江大庆 163000； 2.大庆油田总医院
临床药学科，黑龙江大庆 163316； 3.大庆市人民医院妇产科，黑龙江大庆 163000

收稿日期:2019-06-14 出版日期:2020-07-25 发布日期:2020-07-29
作者简介:贾莹（1986-），女，山东人，硕士，主要从事药学研究工作，E-mail：jy86210@126.com
基金资助:
黑龙江省卫生和计划生育委员会（【2018】129）

The mechanism of Celastrol in inhibiting cell biological behavior of cervical cancer cells

JIA Ying¹, ZHAO Wei¹, ZHANG Xin-yuan², WU Rui³, XIAO Bing-bing¹

1. Daqing Longnan Hospital (the Fifth Hospital of Qiqihar Medical University), Daqing 163000, Heilongjiang Province, China; 2. Department of Clinical Pharmacy, General Hospital of Daqing Oilfield 163316, Heilongjiang Province, China; 3. Department of Obstetrics and Gynecology, Daqing People's Hospital 163000, Heilongjiang Province, China

Received:2019-06-14 Online:2020-07-25 Published:2020-07-29

摘要/Abstract

摘要： 目的　探讨南蛇藤醇抑制宫颈癌细胞增殖和侵袭的作用机制。方法　将正常培养HeLa细胞分为对照组、南蛇藤醇低、中、高剂量组（终浓度分别为4 μmol/L、8 μmol/L和12 μmol/L）、阳性对照组（顺铂，终浓度为10 μmol/L）、LY294002组（LY294002，终浓度为20 μmol/L）和（南蛇藤醇+LY294002）组（南蛇藤醇和LY294002，终浓度分别为12 μmol/L和20 μmol/L）。MTT法检测各组细胞存活情况；流式细胞仪检测细胞凋亡情况；Transwell检测细胞的侵袭；蛋白质印迹法检测PI3K/AKT/NF-κB信号通路的表达；采用皮下注射HeLa细胞建立裸鼠模型，观察南蛇藤醇（120 mg/kg）对裸鼠移植瘤体积和重量的影响。结果　与对照组相比，南蛇藤醇组、阳性对照组和LY294002组HeLa细胞的相对增殖率、侵袭细胞数均明显下降（P<0.001），细胞凋亡率明显升高（P<0.001），p-PI3K、p-AKT、NF-κB p65蛋白表达明显下调（P<0.001），且随着南蛇藤醇浓度升高，其作用增强；与LY294002组相比，（南蛇藤醇+LY294002）组HeLa细胞的相对增殖率和侵袭细胞数明显下降（q=10.182，q=10.217，P均<0.001），细胞凋亡率明显升高（q=23.636，P<0.001）；与对照组相比，南蛇藤醇组裸鼠体重、移植瘤的体积和重量明显下降（q=4.100，P<0.020；q=13.501，P<0.001；q=5.078，P=0.005）。结论　南蛇藤醇可能通过抑制HeLa细胞的PI3K/Akt/NF-κB信号通路，抑制其恶性生物学行为。

关键词: 南蛇藤醇, 　宫颈癌, 　PI3K/AKT/NF-κB信号通路

Abstract: Objective　To explore the mechanism of Celastrol in inhibiting proliferation and invasion ability of cervical cancer cells.　Methods　Normal cultured HeLa cells were divided into the following groups: a control group, a low-dose Celastrol group, a medium-dose Celastrol group and a high-doses Celastrol group (final concentrations of Celastrol were 4 μmol/L, 8 μmol/L and 12 μmol/L, respectively), a positive control group (cisplatin, final concentration of 10 μmol/L), a LY294002 group (LY294002, final concentration of 20 μmol/L) and a Celastrol with LY294002 group ( final concentrations of Celastrol and LY294002 were 12 μmol/L and 20 μmol/L, respectively). The cell survival conditions of each group were detected by MTT assay. The apoptosis of each group were detected by flow cytometry. The cell invasion of each group were detected by Transwell. The expression of PI3K/AKT/NF-κB signaling pathway were detected by Western Blot. HeLa cells were subcutaneously injected to establish nude mice models to observe the effects of Celastrol (120 mg/kg) on volume and weight of transplanted tumors in nude mice.　Results　Compared with the control group, relative proliferation rate of HeLa cells and number of invasive cells in Celastrol group, positive control group and LY294002 group significantly decreased (P<0.001), while apoptosis rates significantly increased (P<0.001), and expression of p-PI3K, p-AKT and NF-κB p65 protein significantly down-regulated (P<0.001). Moreover, with increasing of Celastrol concentration, its effects increased. Compared with the LY294002 group, relative proliferation rate of HeLa cells and number of invasive cells in the Celastrol with LY294002 group significantly decreased (q=10.182, q=10.217; P<0.001), while apoptosis rate significantly increased (q=23.636, P<0.001). Compared with the control group, weight of nude mice, volume and weight of transplanted tumors of nude mice significantly decreased in the Celastrol groups (q=4.100, P<0.020; q=13.501, P<0.001; q=5.078, P=0.005).　Conclusions　Celastrol may inhibit its malignant biological behaviors through inhibiting the PI3K/Akt/NF-κB signaling pathway of HeLa cells

Key words: Celastrol, 　Cervical cancer, 　PI3K/AKT/NF-κB signaling pathway

中图分类号:

R737.33

贾莹, 赵伟, 张欣媛, 吴瑞, 肖兵兵. 南蛇藤醇抑制宫颈癌细胞生物学行为的机制研究[J]. 中国临床解剖学杂志, 2020, 38(4): 421-427.

JIA Ying, ZHAO Wei, ZHANG Xin-yuan, WU Rui, XIAO Bing-bing. The mechanism of Celastrol in inhibiting cell biological behavior of cervical cancer cells [J]. Chinese Journal of Clinical Anatomy, 2020, 38(4): 421-427.

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南蛇藤醇抑制宫颈癌细胞生物学行为的机制研究

The mechanism of Celastrol in inhibiting cell biological behavior of cervical cancer cells

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