5-HT再摄取抑制剂氟西汀诱导HepG2细胞凋亡

肝脏 ›› 2017, Vol. 22 ›› Issue (9): 806-809.

5-HT再摄取抑制剂氟西汀诱导HepG2细胞凋亡

马丽霞, 刘晓慧, 张晶

100069 首都医科大学附属北京佑安医院丙肝与中毒性肝病科

收稿日期:2017-04-26 出版日期:2017-09-30 发布日期:2020-08-03
通讯作者: 张晶,Email: drzhangjing@163.com

5-HT reuptake specific inhibitor fluoxetine induce HepG2 apoptosis

MA Li-xia, Liu Xiao-hui, ZHANG jing

Department of Hepatitis C and Drug-induced liver injury, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China

Received:2017-04-26 Online:2017-09-30 Published:2020-08-03
Contact: ZHANG Jing, Email: drzhangjing@163.com

摘要/Abstract

摘要： 目的通过观察5-HT再摄取特异性抑制剂氟西汀对人肝癌细胞系HepG2细胞凋亡的影响,探索氟西汀治疗肝细胞癌的可能性。方法采用不同浓度氟西汀(5 μmol、7.5 μmol、10 μmol、12.5 μmol、15 μmol)分别处理HepG2细胞24 h、48 h,AnnexinV-FITC/PI 流式细胞术和蛋白水解酶 3免疫荧光法检测细胞凋亡。结果 10 μmol、12.5 μmol氟西汀处理24 h早期凋亡率分为(14.41±5.40)%、(19.43±5.91)%,与对照组(4.05±1.90)%相比差异均具有统计学意义(均P<0.05).5 μmol氟西汀处理48 h早期凋亡率为(20.32±6.23)%,与对照组(12.40±4. 18)%相比差异有统计学意义(均P<0.05),10 μmol及12.5 μmol 氟西汀处理24 h活化caspase3阳性细胞显著增加。结论氟西汀具有促进HepG2细胞凋亡的作用,为临床上应用氟西汀治疗肝细胞癌患者提供了依据。

关键词: HepG2细胞, 氟西汀, 凋亡, 肝细胞癌

Abstract: ObjectiveTo investigate the effect of 5-hydroxytryptamine (5-HT) reuptake specific inhibitor fluoxetine on apoptosis of human hepatocellular carcinoma cell line (HepG2). Methods HepG2 cells were treated with different concentrations of fluoxetine (5 μM, 7.5 μM, 10 μM, 12.5 μM, 15 μM) for 24 h and 48 h, respectively. Apoptosis was detected using Annexin V-FITC/PI flow cytometry and proteolytic enzyme 3 immunofluorescence assay. Results The 24 h apoptosis rates of HepG2 treated with 10 μM and 12.5 μM fluoxetine were 14.41%±5.40% and 19.43%±5.91%, which were significantly higher than that with control treatment (4.05%±1.90%, both P<0.05 )，respectively. The apoptosis rate was 20. 32%±6. 23% after 48 h treatment with 5 μM fluoxetine, which was significantly higher than that with control treatment (12. 40%±4.18%，P<0. 05). Treatment with 10 μM or 12. 5 μM fluoxetine for 24 h significantly increased activated caspase 3 positive cells. ConclusionFluoxetine could promote the apoptosis of HepG2 cells in a dose-dependent manner, which provides a clue for the clinical application of fluoxetine in the treatment of patients with hepatocellular carcinoma.

Key words: HepG2 cells, Fluoxetine, Apoptosis, Hepatocellular carcinoma

马丽霞, 刘晓慧, 张晶. 5-HT再摄取抑制剂氟西汀诱导HepG2细胞凋亡[J]. 肝脏, 2017, 22(9): 806-809.

MA Li-xia, Liu Xiao-hui, ZHANG jing. 5-HT reuptake specific inhibitor fluoxetine induce HepG2 apoptosis[J]. Chinese Hepatolgy, 2017, 22(9): 806-809.

参考文献

[1] Ferlay J, Soerjomataram I, Ervik M, et al. Cancer incidence and mortality worldwide: sources, methods and maior pattems in GLOBOCAN 2012. Int J cancer, 2015, 136: E359-E386.
[2] Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J CIin, 2012, 62: 394-399.
[3] Bruix J,Sherman M. Managements of hepatocellar carcinoma: an update. Hepatology, 2011, 53: 1020-1022.
[4] Gish RG. Hepatocellular carcinoma: overcoming challenges in disease management. Clin Gastroenterol Hepatol, 2006, 4: 252-261.
[5] Zaanan A, Williet N, Hebbar M, et al. Gemcitabine plus oxaliplatin in advanced hetaocelluar carcinoma: a large multicenter AGEO study. J Hepatol, 2012, 58: 81-88.
[6] Brandes LJ, Arron RJ, Bogdanovic RP, et al. Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. Cancer Res, 1992, 52: 3796-3800.
[7] Stepulak A, Rzeski W, Sifringer M, et al. Fluoxetine inhibits the extracellular signal regulated kinase pathway and suppresses growth of cancer cells. Cancer Biol Ther, 2008, 7: 1685-1693.
[8] Zhou T, Duan J, Wang Y, et al. Fluoxetine synergys with anticancer drugs to overcome multidrug resistance in breast cancer cells. Tumor Biol, 2012, 33:1299-1306.
[9] Frick LR, Rapanelli M, Arcos ML, et al. Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice. Eur J Pharmacol, 2011, 659: 265-272.
[10] Wong DT, Bymaster FP, Engleman EA.Prozac (fluoxetine, Lilly 110140),the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci, 1995, 57:411-441.
[11] Serafeim A, Holder MJ, Grafton G, et al.Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells.Blood, 2003,101: 3212-3219.
[12] Mun AR, Lee SJ, Kim GB, et al.Fluoxetine induced apoptosis in hepatocellular carcinoma cells. Anticancer Res, 2013, 33:3691-3697.
[13] Chan SL,Yeo W.Targeted therapy of hepatocellular carcinoma: present and future.J Gastroenterol Hepatol, 2012, 27:862-872.
[14] 刘琳,郑英慧,韩力,等.含奥沙利铂系统化疗方案治疗晚期原发性肝癌有效性和安全性的前瞻性研究荟萃分析. 临床肿瘤学杂志,2015, 20:769-779.
[15] Yau T, Chan P, Epstein R, et al.Management of advanced hepatocellular carcinoma in the era of targeted therapy. Liver Int, 2009, 29: 10-17.
[16] Cheng AL, Kang YK, Chen Z, et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:a phase III randomized, double blind, placebo controlled trial.Lancet Oncol, 2009, 10: 25-34.
[17] Zheng T, Yin D, Lu Z, et al.Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant P53 in hepatocelluar carcinoma. Mol Cancer, 2014, 13: 133-144.
[18] Zhu AX, Kudo M, Assenat E, et al.Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 andomized clinical trial. JAMA, 2014, 312: 57-67.