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.肝癌干細胞與肝癌的研究進展.中國癌癥雜志, 2011, 21(9):735-738.
2.	孫燕, 屠紅, 陸培新, 等.肝癌家族史與肝癌關系的20年前瞻性隊列研究.中華肝臟病雜志, 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.	張浩, 余侃儒, 石偉, 等.肝癌抑制因子1在肝癌組織中的表達與臨床意義.中華實驗外科雜志, 2012, 29(10):1899-1901.
5.	張克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9與肝細胞肝癌浸潤轉移的實驗研究.中華肝膽外科雜志, 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.	張俊峰, 陳規劃, 陸敏強, 等.線粒體在雷帕霉素誘導肝癌細胞Bel-7402凋亡中的作用.中國普外基礎與臨床雜志, 2007, 14(3):280-283.
12.	黃煜倫, 周幽心, 周岱, 等.雷公藤紅素抑制血管生成的實驗研究.中華腫瘤雜志, 2003, 5(25):429-432.
13.	張杰, 廖啟順, 王蘭瓊.國內雷公藤紅素藥理作用及臨床運用研究概況.中國民族民間醫藥雜志, 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.	丁海鵬, 李相鵬, 張偉, 等.雷公藤紅素藥理作用分子靶點的研究進展.中國藥理學與毒理學雜志, 2012, 26(4):570-576.
17.	黃斌, 李昂, 張波, 等.納米炭吸附5-FU淋巴靶向化療對胃癌組織及轉移淋巴結bcl-2、bax及caspase-3表達的影響.中國普外基礎與臨床雜志, 2009, 16(1):18-22.
18.	張金龍, 李艷飛, 王奔, 等.維生素E缺乏對雛雞脾臟淋巴細胞Caspase-3活性及Caspase-3 mRNA表達的影響.中國獸醫學報, 2008, 12(28):1438-1440.
19.	陳俊, 唐安洲, 梁鋼, 等.苦參堿改構體X調控Caspase-3, Caspase-8和Caspase-9蛋白表達誘導人鼻咽癌CNE1凋亡的研究.中國藥理學通報, 2013, 8(29):1136-1140.
20.	侯燕, 朱斌, 劉堅.呼吸道合胞病毒誘導a549細胞凋亡與nf-Kb信號通路有關.基礎醫學與臨床, 2013, 10(33):1288-1292.
21.	洪良利, 秦杰升, 黃杰雄, 等. NF-κB p65、CyclinD1在甲狀腺乳頭狀癌組織中的表達及意義.海南醫學, 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.	鄔林泉, 戈華平, 羅志強, 等. NF-кB與P-gp在肝細胞肝癌組織中的表達.中華肝膽外科雜志, 2007, 13(5):314-316.
25.	張克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9與肝細胞肝癌浸潤轉移的實驗研究.中華肝膽外科雜志, 2006, 12(10):691-694.

1. 王英.肝癌干細胞與肝癌的研究進展.中國癌癥雜志, 2011, 21(9):735-738.
2. 孫燕, 屠紅, 陸培新, 等.肝癌家族史與肝癌關系的20年前瞻性隊列研究.中華肝臟病雜志, 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. 張浩, 余侃儒, 石偉, 等.肝癌抑制因子1在肝癌組織中的表達與臨床意義.中華實驗外科雜志, 2012, 29(10):1899-1901.
5. 張克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9與肝細胞肝癌浸潤轉移的實驗研究.中華肝膽外科雜志, 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. 張俊峰, 陳規劃, 陸敏強, 等.線粒體在雷帕霉素誘導肝癌細胞Bel-7402凋亡中的作用.中國普外基礎與臨床雜志, 2007, 14(3):280-283.
12. 黃煜倫, 周幽心, 周岱, 等.雷公藤紅素抑制血管生成的實驗研究.中華腫瘤雜志, 2003, 5(25):429-432.
13. 張杰, 廖啟順, 王蘭瓊.國內雷公藤紅素藥理作用及臨床運用研究概況.中國民族民間醫藥雜志, 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. 丁海鵬, 李相鵬, 張偉, 等.雷公藤紅素藥理作用分子靶點的研究進展.中國藥理學與毒理學雜志, 2012, 26(4):570-576.
17. 黃斌, 李昂, 張波, 等.納米炭吸附5-FU淋巴靶向化療對胃癌組織及轉移淋巴結bcl-2、bax及caspase-3表達的影響.中國普外基礎與臨床雜志, 2009, 16(1):18-22.
18. 張金龍, 李艷飛, 王奔, 等.維生素E缺乏對雛雞脾臟淋巴細胞Caspase-3活性及Caspase-3 mRNA表達的影響.中國獸醫學報, 2008, 12(28):1438-1440.
19. 陳俊, 唐安洲, 梁鋼, 等.苦參堿改構體X調控Caspase-3, Caspase-8和Caspase-9蛋白表達誘導人鼻咽癌CNE1凋亡的研究.中國藥理學通報, 2013, 8(29):1136-1140.
20. 侯燕, 朱斌, 劉堅.呼吸道合胞病毒誘導a549細胞凋亡與nf-Kb信號通路有關.基礎醫學與臨床, 2013, 10(33):1288-1292.
21. 洪良利, 秦杰升, 黃杰雄, 等. NF-κB p65、CyclinD1在甲狀腺乳頭狀癌組織中的表達及意義.海南醫學, 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. 鄔林泉, 戈華平, 羅志強, 等. NF-кB與P-gp在肝細胞肝癌組織中的表達.中華肝膽外科雜志, 2007, 13(5):314-316.
25. 張克君, 李德春, 高焱明, 等. Nf-κb、Mmp-9與肝細胞肝癌浸潤轉移的實驗研究.中華肝膽外科雜志, 2006, 12(10):691-694.

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