异丙酚通过抑制NF-κB信号通路促进肝癌HepG2细胞凋亡-现代医学

异丙酚通过抑制NF-κB信号通路促进肝癌HepG2细胞凋亡

单位：1. 成都市第三人民医院麻醉科, 四川成都 610031;
2. 重庆医科大学基础医学院生理学教研室, 重庆 401331;
3. 成都市第三人民医院肿瘤科, 四川成都 610031

分类号：Q291

出版年·卷·期（页码）：2020·48·第十二期（1582-1588）

摘要：

目的： 探讨异丙酚对人肝癌HepG2细胞增殖抑制和凋亡诱导的作用及对核转录因子κB （NF-κB）信号通路的影响。方法： 利用噻唑蓝（MTT）比色法检测不同浓度的异丙酚在不同时间点对肝癌HepG2细胞增殖的影响，流式细胞术检测不同浓度的异丙酚诱导HepG2细胞凋亡情况，采用蛋白免疫印迹（Western blotting）法检测不同浓度的异丙酚对HepG2细胞中增殖细胞核抗原（PCNA）、剪切的含半胱氨酸的天冬氨酸蛋白水解酶3（cleaved caspase-3）及NF-κB信号通路的活性。在异丙酚干预的HepG2细胞中添加NF-κB信号通路激活剂重组人TNF-α，采用同样的方法检测HepG2细胞增殖和凋亡情况。结果： MTT实验数据显示，随着异丙酚浓度的增加及作用时间的延长，其对HepG2细胞增殖能力的抑制作用逐渐升高，此外，异丙酚还可抑制增殖相关蛋白PCNA的表达。流式细胞术结果显示，异丙酚可促进细胞凋亡，且凋亡相关蛋白Cleaved Caspase-3的表达显著升高。Western blotting检测结果显示异丙酚能够降低NF-κB p65和IκBα的磷酸化水平，有效抑制了NF-κB信号通路的激活。添加NF-κB信号通路激活剂TNF-α能够有效逆转异丙酚所致的HepG2细胞增殖抑制和凋亡增加。结论： 异丙酚能够通过抑制NF-κB信号通路的激活抑制肝癌HepG2细胞增殖及促进细胞凋亡。

Objective: To investigate the effects of propofol on proliferation inhibition and apoptosis induction of human hepatoma HepG2 cells and nuclear factor kappa B (NF-κB) signaling pathway. Methods: The effect of different concentrations of propofol on the proliferation of HepG2 cells at different time points was detected by MTT assay. Flow cytometry was used to detect the apoptosis of HepG2 cells induced by different concentrations of propofol. The activity of different concentrations of propofol on the proliferating cell nuclear antigens (PCNA), cleaved caspase-3 and NF-κB signaling pathways in HepG2 cells were detected by Western blotting. The recombinant human TNF-α which is the NF-κB signaling pathway activator was added to the HepG2 cells treated with propofol. The proliferation and apoptosis of HepG2 cells were detected by the same methods. Results: MTT assay showed that the inhibitory effect on the proliferation of HepG2 cells gradually increased with the increase of the concentration of propofol and the extension of the action time. In addition, propofol can also inhibit the expression of the proliferation-related protein PCNA. Flow cytometry results showed that propofol could promote cell apoptosis, and the expression of apoptosis-related protein cleaved caspase-3 was significantly increased. Western blotting test also showed that propofol can reduce the phosphorylation of NF-κB p65 and IκBα, and inhibit the activation of NF-κB signaling pathway effectively. TNF-α which is NF-κB signaling pathway activator can reverse the proliferation inhibition and apoptosis of HepG2 cells induced by propofol effectively. Conclusion: Propofol can inhibit the proliferation of liver cancer HepG2 cells and promote cell apoptosis by inhibiting the activation of NF-κB signaling pathway.

参考文献：

[1] MOMIN B,MILLMAN A J,NIELSEN D B,et al.Promising practices for the prevention of liver cancer:a review of the literature and cancer plan activities in the national comprehensive cancer control program[J].Cancer Causes Control,2018,29(12):1265-1275.
[2] 田小强,鲁世慧,王礼学,等.不可手术的原发性肝癌放疗效果影响因素及预后分析[J].东南大学学报(医学版),2019,38(6):1029-1034.
[3] KIM R.Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence[J].J Transl Med,2018,16(1):8-20.
[4] VAHABI S,EATEMADI A.Effects of anesthetic and analgesic techniques on cancer metastasis[J].Biomed Pharmacother,2017,87:1-7.
[5] FENG A Y,KAYE A D,KAYE R J,et al.Novel propofol derivatives and implications for anesthesia practice[J].J Anaesthesiol Clin Pharmacol,2017,33(1):9-15.
[6] 盘诗芮,黄焕森,卢国安,等.异丙酚对人肝癌细胞侵袭转移能力及上皮间质转化的影响[J].广东医学,2018,39(10):1449-1453.
[7] LIU W Z,LIU N.Propofol inhibits lung cancer A549 cells growth and epithelial-mesenchymal transition process by up-regulation of microRNA-1284[J].Oncol Res,2018,27(1):1-8.
[8] GRINBERGBLEYER Y,OH H,DESRICHARD A,et al.NF-κB c-rel is crucial for the regulatory T cell immune checkpoint in cancer[J].Cell,2017,170(6):1096-1108.
[9] WANG S,LIANG S,ZHAO X,et al.Propofol inhibits cell proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes via the nuclear factor-κB pathway[J].Am J Transl Res,2017,9(5):2429-2436.
[10] YANG Z,CHENG F,YAN G,et al.Propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation[J].Exp Ther Med,2018,15(2):2032-2036.
[11] HUANG X,TENG Y,YANG H,et al.Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-κB signal[J].Braz J Med Biol Res,2016,49(12):e5717.
[12] BYRNE K,LEVINS K J,BUGGY D J.Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis?[J].Can J Anaesth,2016,63(2):1-9.
[13] YANG N,LIANG Y,YANG P,et al.Propofol inhibits lung cancer cell viability and induces cell apoptosisby upregulating microRNA-486 expression[J].Braz J Med Biol Res,2017,50(1):e5794.
[14] YU B,GAO W,ZHOU H,et al.Propofol induces apoptosis of breast cancer cells by downregulation of miR-24 signal pathway[J].Cancer Biomark,2018,21(3):513-519.
[15] 闵娜,胡强夫,张韶南,等.异丙酚通过Wnt/β-catenin信号通路对HepG2细胞表达抑制作用的研究[J].实用糖尿病杂志,2017(3):45-46.
[16] 周桥灵,刘洪珍,杨敏清,等.PI3K/Akt信号通路在异丙酚抑制人肝癌细胞侵袭中的作用[J].中华麻醉学杂志,2018,38(1):110-113.
[17] OZTURK M,BATUR T,EKIN U,et al.Molecular pathogenesis of liver cancer[J].J Gastrointest Cancer,2017,48(3):1-3.
[18] CHOE K N,MOLDOVAN G L.Forging ahead through darkness:PCNA,still the principal conductor at the replication fork[J].Mol Cell,2017,65(3):380-392.
[19] FREIRE R,FAGAGNA F D D,WU L,et al.Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase Ⅲα[J].Nucleic Acids Res,2017,29(15):3172-3180.
[20] 陈果,李波.原发性肝癌分子信号通路及靶向药物的研究进展[J].现代医药卫生,2017,33(8):61-65.
[21] 徐新明,陈健,陆荣柱,等.姜黄素通过内质网应激信号通路诱导肝癌SMMC-7721细胞凋亡的作用研究[J].东南大学学报(医学版),2018,37(1):12-17.
[22] 朱倩,卢贵余,桂芬芳,等.TNF-α对肝癌细胞NF-κB信号通路活化的影响及临床意义[J].河北医药,2018,40(24):21-24.
[23] Ma D Q,Zhang Y H,Ding D P,et al.Effect of Bmi-1-mediated NF-κB signaling pathway on the stem-like properties of CD133⁺ human liver cancer cells[J].Cancer Biomark,2018,22(3):1-11.
[24] MAJIDINIA M,ALIZADEH E,YOUSEFI B,et al.Co-inhibition of notch and NF-κB signaling pathway decreases proliferation through downregulating IκB-α and Hes-1 expression in human ovarian cancer OVCAR-3 cells[J].Drug Res,2017,67(1):13-19.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录