Apoptosis of Human Hepatocellular Carcinoma Cell Line SMMC-7721 Induced by The Celastrol_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANGYi-chuan , LIUFeng , WANGJun , XUJie , YANGMao-hui , LIJin

Department of Hepato-biliary-pancreatic-splenic Surgery, Affiliated Hospital of Panzhihua College, Panzhihua 617000, Sichuan Province, China;

Corresponding author：

ZHANGYi-chuan, Email: YCZhang_KY@163.com

Keywords：

Celastrol; Hepatoma cell; Caspase-3; NF-κB protein

DOI：

10.7507/1007-9424.20160013

Video：

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Objective To investigate the effects of celastrol on the growth and apoptosis of huamn hepatoma SMMC-7721 cells, and investigate its preliminary action mechansim. Methods SMMC-7721 cells were cultured in vitro, CCK-8 assay and Annexin V-FITC/PI staining method were conducted to investigate the effects of celastrol on the growth and apoptosis of huamn hepatoma SMMC-7721 cells after the cells were treated with drugs, and then the Caspase-3 activity and NF-κB protein expression were determined by Caspase-3 activity determination kit and Western blot. Huamn hepatoma SMMC-7721 cells transplantation tumor models in nude mice were established and the effect of celastrol on the growth of transplantation tumor were observed. Results Celastrol could inhibit the SMMC-7721 cells growth in a dose and time dependent manner. Annexin-V/PI staining showed that SMMC-7721 cells were induced to death with the concentration increasing of celastrol. Caspase-3 activity was measured after treatment with celastrol and the results indicated that the activity of caspase-3 was significantly enhanced. Western blot experiments showed that the expression of NF-κB protein decreased in a time-dependent manner after treatment with celastrol. Celastrol could inhibit SMMC-7721 cells transplantation tumor growth in nude mice. Conclusions Celastrol could inhibit the proliferation of human hepatoma SMMC-7721 cells and induces apoptosis, and inhibit SMMC-7721 cell transplantation tumor growth in nude mice. Celastrol induce apoptosis of SMMC-7721 cells might through activating Caspase-3 pathway and NF-κB pathway.

Citation： ZHANGYi-chuan, LIUFeng, WANGJun, XUJie, YANGMao-hui, LIJin. Apoptosis of Human Hepatocellular Carcinoma Cell Line SMMC-7721 Induced by The Celastrol. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(1): 48-51. doi: 10.7507/1007-9424.20160013 Copy

1.	王英.肝癌干细胞与肝癌的研究进展.中国癌症杂志, 2011, 21(9):735-738.
2.	孙燕, 屠红, 陆培新, 等.肝癌家族史与肝癌关系的20年前瞻性队列研究.中华肝脏病杂志, 2014, 22(10):752-756.
3.	Hsu YC, Wu CY, Lin JT. Hepatitis C virus infection, antiviral therapy, and risk of hepatocellular carcinoma. Semin Oncol, 2015, 42(2):329-338.
4.	张浩, 余侃儒, 石伟, 等.肝癌抑制因子1在肝癌组织中的表达与临床意义.中华实验外科杂志, 2012, 29(10):1899-1901.
5.	张克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9与肝细胞肝癌浸润转移的实验研究.中华肝胆外科杂志, 2006, 12(10):691-694.
6.	Dai Y, Desano J, Tang W, et al. Natural proteasome inhibitor celastrol suppresses androgen-independent prostate cancer progres-sion by modulating apoptotic proteins and NF-kappaB. PLoS One, 2010, 5(12):e14153.
7.	Ji N, Li J, Wei Z, et al. Effect of celastrol on growth inhibition of prostate cancer cells through the regulation of hERG channel in vitro. Biomed Res Int, 2015, 2015:308475.
8.	Shrivastava S, Jeengar MK, Reddy VS, et al. Anticancer effect of celastrol on human triple negative breast cancer:Possible involve-ment of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways. Exp Mol Pathol, 2015, 98(3):313-327.
9.	Kim K. Interaction between HSP 70 and iNOS in skeletal muscle injury and repair. Journal of exercise rehabilitation, 2015, 11(5):240-243.
10.	Kim MN, Han KH, Ahn SH. Prevention of hepatocellular carcinoma:beyond hepatitis B vaccination. Semin Oncol, 2015, 42(2):316-328.
11.	张俊峰, 陈规划, 陆敏强, 等.线粒体在雷帕霉素诱导肝癌细胞Bel-7402凋亡中的作用.中国普外基础与临床杂志, 2007, 14(3):280-283.
12.	黄煜伦, 周幽心, 周岱, 等.雷公藤红素抑制血管生成的实验研究.中华肿瘤杂志, 2003, 5(25):429-432.
13.	张杰, 廖启顺, 王兰琼.国内雷公藤红素药理作用及临床运用研究概况.中国民族民间医药杂志, 2005, 74:128-132.
14.	Yang H, Chen D, Cui QC, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine, " is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66(9):4758-4765.
15.	Yoon MJ, Lee AR, Jeong SA, et al. Release of Ca2+ from the endoplasmic reticulum and its subsequent influx into mitochondria trigger celastrol-induced paraptosis in cancer cells. Oncotarget, 2014, 5(16):6816-6831.
16.	丁海鹏, 李相鹏, 张伟, 等.雷公藤红素药理作用分子靶点的研究进展.中国药理学与毒理学杂志, 2012, 26(4):570-576.
17.	黄斌, 李昂, 张波, 等.纳米炭吸附5-FU淋巴靶向化疗对胃癌组织及转移淋巴结bcl-2、bax及caspase-3表达的影响.中国普外基础与临床杂志, 2009, 16(1):18-22.
18.	张金龙, 李艳飞, 王奔, 等.维生素E缺乏对雏鸡脾脏淋巴细胞Caspase-3活性及Caspase-3 mRNA表达的影响.中国兽医学报, 2008, 12(28):1438-1440.
19.	陈俊, 唐安洲, 梁钢, 等.苦参碱改构体X调控Caspase-3, Caspase-8和Caspase-9蛋白表达诱导人鼻咽癌CNE1凋亡的研究.中国药理学通报, 2013, 8(29):1136-1140.
20.	侯燕, 朱斌, 刘坚.呼吸道合胞病毒诱导a549细胞凋亡与nf-Kb信号通路有关.基础医学与临床, 2013, 10(33):1288-1292.
21.	洪良利, 秦杰升, 黄杰雄, 等. NF-κB p65、CyclinD1在甲状腺乳头状癌组织中的表达及意义.海南医学, 2014, 25(12):1853-1855.
22.	Nabekura T, Hiroi T, Kawasaki T, et al. Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein. Biomed Pharmacother, 2015, 70:140-145.
23.	Yang H, Chen D, Cui QC, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine, " is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66(9):4758-4765.
24.	邬林泉, 戈华平, 罗志强, 等. NF-кB与P-gp在肝细胞肝癌组织中的表达.中华肝胆外科杂志, 2007, 13(5):314-316.
25.	张克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9与肝细胞肝癌浸润转移的实验研究.中华肝胆外科杂志, 2006, 12(10):691-694.

1. 王英.肝癌干细胞与肝癌的研究进展.中国癌症杂志, 2011, 21(9):735-738.
2. 孙燕, 屠红, 陆培新, 等.肝癌家族史与肝癌关系的20年前瞻性队列研究.中华肝脏病杂志, 2014, 22(10):752-756.
3. Hsu YC, Wu CY, Lin JT. Hepatitis C virus infection, antiviral therapy, and risk of hepatocellular carcinoma. Semin Oncol, 2015, 42(2):329-338.
4. 张浩, 余侃儒, 石伟, 等.肝癌抑制因子1在肝癌组织中的表达与临床意义.中华实验外科杂志, 2012, 29(10):1899-1901.
5. 张克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9与肝细胞肝癌浸润转移的实验研究.中华肝胆外科杂志, 2006, 12(10):691-694.
6. Dai Y, Desano J, Tang W, et al. Natural proteasome inhibitor celastrol suppresses androgen-independent prostate cancer progres-sion by modulating apoptotic proteins and NF-kappaB. PLoS One, 2010, 5(12):e14153.
7. Ji N, Li J, Wei Z, et al. Effect of celastrol on growth inhibition of prostate cancer cells through the regulation of hERG channel in vitro. Biomed Res Int, 2015, 2015:308475.
8. Shrivastava S, Jeengar MK, Reddy VS, et al. Anticancer effect of celastrol on human triple negative breast cancer:Possible involve-ment of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways. Exp Mol Pathol, 2015, 98(3):313-327.
9. Kim K. Interaction between HSP 70 and iNOS in skeletal muscle injury and repair. Journal of exercise rehabilitation, 2015, 11(5):240-243.
10. Kim MN, Han KH, Ahn SH. Prevention of hepatocellular carcinoma:beyond hepatitis B vaccination. Semin Oncol, 2015, 42(2):316-328.
11. 张俊峰, 陈规划, 陆敏强, 等.线粒体在雷帕霉素诱导肝癌细胞Bel-7402凋亡中的作用.中国普外基础与临床杂志, 2007, 14(3):280-283.
12. 黄煜伦, 周幽心, 周岱, 等.雷公藤红素抑制血管生成的实验研究.中华肿瘤杂志, 2003, 5(25):429-432.
13. 张杰, 廖启顺, 王兰琼.国内雷公藤红素药理作用及临床运用研究概况.中国民族民间医药杂志, 2005, 74:128-132.
14. Yang H, Chen D, Cui QC, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine, " is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66(9):4758-4765.
15. Yoon MJ, Lee AR, Jeong SA, et al. Release of Ca2+ from the endoplasmic reticulum and its subsequent influx into mitochondria trigger celastrol-induced paraptosis in cancer cells. Oncotarget, 2014, 5(16):6816-6831.
16. 丁海鹏, 李相鹏, 张伟, 等.雷公藤红素药理作用分子靶点的研究进展.中国药理学与毒理学杂志, 2012, 26(4):570-576.
17. 黄斌, 李昂, 张波, 等.纳米炭吸附5-FU淋巴靶向化疗对胃癌组织及转移淋巴结bcl-2、bax及caspase-3表达的影响.中国普外基础与临床杂志, 2009, 16(1):18-22.
18. 张金龙, 李艳飞, 王奔, 等.维生素E缺乏对雏鸡脾脏淋巴细胞Caspase-3活性及Caspase-3 mRNA表达的影响.中国兽医学报, 2008, 12(28):1438-1440.
19. 陈俊, 唐安洲, 梁钢, 等.苦参碱改构体X调控Caspase-3, Caspase-8和Caspase-9蛋白表达诱导人鼻咽癌CNE1凋亡的研究.中国药理学通报, 2013, 8(29):1136-1140.
20. 侯燕, 朱斌, 刘坚.呼吸道合胞病毒诱导a549细胞凋亡与nf-Kb信号通路有关.基础医学与临床, 2013, 10(33):1288-1292.
21. 洪良利, 秦杰升, 黄杰雄, 等. NF-κB p65、CyclinD1在甲状腺乳头状癌组织中的表达及意义.海南医学, 2014, 25(12):1853-1855.
22. Nabekura T, Hiroi T, Kawasaki T, et al. Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein. Biomed Pharmacother, 2015, 70:140-145.
23. Yang H, Chen D, Cui QC, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine, " is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66(9):4758-4765.
24. 邬林泉, 戈华平, 罗志强, 等. NF-кB与P-gp在肝细胞肝癌组织中的表达.中华肝胆外科杂志, 2007, 13(5):314-316.
25. 张克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9与肝细胞肝癌浸润转移的实验研究.中华肝胆外科杂志, 2006, 12(10):691-694.

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