三氧化二砷治疗原发性肝细胞癌的实验及临床研究进展
Experimental and Clinical Research Progress of Arsenic Trioxide in Treating Hepatocellular Carcinoma
DOI: 10.12677/TCM.2020.91006, PDF,    国家自然科学基金支持
作者: 万迁迁, 万旭英：海军军医大学第三附属医院中西医结合科，上海
关键词: 原发性肝细胞癌；三氧化二砷；研究进展；Hepatocellular Carcinoma； Arsenic Trioxide； Research Progress
摘要: 原发性肝细胞癌(Hepatocellular Carcinoma, HCC)的发病率在全世界呈上升趋势，三氧化二砷(Arsenic trioxide, As2O3)，作为一种中药单体，已经被大量用于HCC的实验及临床研究。但仍需要大样本的临床研究来明确其临床疗效，仍有必要进行As2O3联合TACE、化疗药物及靶向药物等治疗原发性肝癌的临床研究。
Abstract: The incidence of Hepatocellular Carcinoma (HCC) is on the rise worldwide. Arsenic trioxide (As2O3), as a monomer of traditional Chinese medicine, has been widely used in experimental and clinical studies of HCC. However, large samples of clinical studies are still needed to clarify its clinical efficacy, and clinical studies on combination of As2O3 with TACE, chemotherapy drugs and targeted drugs for the treatment of primary liver cancer are still necessary.
文章引用：万迁迁, 万旭英. 三氧化二砷治疗原发性肝细胞癌的实验及临床研究进展[J]. 中医学, 2020, 9(1): 34-39. https://doi.org/10.12677/TCM.2020.91006

参考文献

[1] Vogel, A., Cervantes, A., Chau, I., Daniele, B., Llovet, J., Meyer, T., Nault, J.C., Neumann, U., Ricke, J., Sangro, B., Schirmacher, P., Verslype, C., Zech, C.J., Arnold, D. and Martinelli, E. (2018) Hepatocellular Carcinoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 29, iv238-iv55. [Google Scholar] [CrossRef] [PubMed]
[2] 余炯杰, 严文韬, 权冰, 杨田. “2018年欧洲肝病学会临床实践指南: 肝细胞癌的管理”推荐意见[J]. 临床肝胆病杂志, 2018, 34(6): 1183-1186.
[3] 葛宁灵, 薛同春, 叶胜龙. “2018年欧洲肝病学会临床实践指南: 肝细胞癌的管理”解读[J]. 临床肝胆病杂志, 2018, 34(6): 1187-1190.
[4] 倪建华, 陈国强, 沈志祥, 李秀松, 刘海卫, 黄燕婷, 方智雯, 陈赛娟, 王振义, 陈竺. 静脉滴注三氧化二砷治疗急性早幼粒细胞白血病的药代动力学分析[J]. 中华血液学杂志, 1997(5): 27-30.
[5] Shen, Z.X., Chen, G.Q., Ni, J.H., Li, X.S., Xiong, S.M., Qiu, Q.Y., Zhu, J., Tang, W., Sun, G.L., Yang, K.Q., Chen, Y., Zhou, L., Fang, Z.W., Wang, Y.T., Ma, J., Zhang, P., Zhang, T., Chen, S.J., Chen, Z. and Wang, Z.Y. (1997) Use of Arsenic Trioxide (As2O3) in the Treatment of Acute Promyelocytic Leukemia (APL): II. Clinical Efficacy and Pharmacokinetics in Relapsed Patients. Blood, 89, 3354-3360. [Google Scholar] [CrossRef] 
[6] Ni, J., Chen, G., Shen, Z., Li, X., Liu, H., Huang, Y., Fang, Z., Chen, S., Wang, Z. and Chen, L. (1997) Pharmacokinetics of Intravenous Arsenic Trioxide in the Treatment of Acute Promyelocytic Leukemia. Chinese Journal of Hematology, 18, 250-253.
[7] 刘琳, 秦叔逵, 陈惠英, 王锦鸿, 陈洪, 马军, 刘文虎. 三氧化二砷选择性诱导人肝癌细胞凋亡及相关基因的实验研究[J]. 中华肝脏病杂志, 2000, 8(6): 367-379.
[8] 王纪渊, 丁国善. 三氧化二砷治疗肝癌的研究进展[J]. 中国普通外科杂志, 2014, 23(1): 102-105.
[9] 邱从坤, 陈国硕, 王忠富, 周志鹏, 汤日杰. 三氧化二砷治疗肝癌的研究进展[J]. 中华介入放射学电子杂志. 2015, 3(1): 52-55.
[10] 张靖宇, 刘宝刚. 三氧化二砷在抗肝癌中的研究进展[J]. 实用肿瘤学杂志, 2008, 22(2): 192-194.
[11] Alarifi, S., Ali, D., Alkahtani, S., Siddiqui, M.A. and Ali, B.A. (2013) Arsenic Tri-oxide-Mediated Oxidative Stress and Genotoxicity in Human Hepatocellular Carcinoma Cells. OncoTargets and therapy, 6, 75-84. [Google Scholar] [CrossRef] 
[12] Liu, B., Pan, S., Dong, X., Qiao, H., Jiang, H., Krissansen, G.W. and Sun, X. (2006) Opposing Effects of Arsenic Trioxide on Hepatocellular Carcinomas in Mice. Cancer Science, 97, 675-681. [Google Scholar] [CrossRef] [PubMed]
[13] 李海燕, 曹励民, 王娟. 三氧化二砷对人肝癌SMMC-7721细胞增殖、迁移及侵袭能力的影响[J]. 中国老年学杂志, 2013, 33(11): 2572-2574.
[14] 金洲祥, 王向昱. 三氧化二砷联合5-氟尿嘧啶对小鼠肝癌H22细胞株的抑制作用[J]. 温州医学院学报, 2013, 43(10): 655-659.
[15] 刘玉. As2O3联合AZT抗HepG2细胞的协同作用研究[D]: [硕士学位论文]. 兰州: 甘肃中医药大学, 2015.
[16] 嵇静. 三氧化二砷与顺铂联用对肝癌HepG2细胞的作用[J]. 临床医药实践, 2009, 18(13): 331-333.
[17] Sadaf, N., Kumar, N., Ali, M., Ali, V., Bimal, S. and Haque, R. (2018) Arsenic Trioxide Induces Apoptosis and Inhibits the Growth of Human Liver Cancer Cells. Life Sciences, 205, 9-17. [Google Scholar] [CrossRef] [PubMed]
[18] Zhao, W., Hu, Y.N., Jiang, X.J., Chen, C.Z. and Zhang, Z.Z. (2014) The Apoptotic Mechanism of Hepatocellular Carcinoma Cell Line (HepG2) Induced by Arsenic Trioxide. Journal of Sichuan University Medical Science Edition, 45, 739-743.
[19] 于浩, 姜洪磊, 许东, 梁健. 三氧化二砷对不同肝癌细胞系凋亡的影响[J]. 生物医学工程与临床, 2016, 20(1): 83-86.
[20] Wang, L., Min, Z., Wang, X., Hu, M., Song, D., Ren, Z., Cheng, Y. and Wang, Y. (2018) Arsenic Trioxide and Sorafenib Combination Therapy for Human Hepatocellular Carcinoma Functions via up-Regulation of TNF-Related Apoptosis-Inducing Ligand. Oncology Letters, 16, 3341-3350. [Google Scholar] [CrossRef] [PubMed]
[21] 段建华, 陈鉴, 钱燕敏, 马良. 三氧化二砷对肝癌细胞表达PTTG1和VEGF的影响及其意义[J]. 国际消化病杂志, 2012, 32(2): 114-117.
[22] 宋海林, 王雪雯, 段晶晶, 周明, 杨莉. 三氧化二砷对肝癌HepG2细胞形成血管生成拟态的影响及其机制[J]. 吉林大学学报(医学版), 2014, 40(4): 715-719+914.
[23] 高明, 褚成静, 王雪雯. 不同浓度三氧化二砷对肝癌细胞生长及血管内皮生长因子表达的影响[J]. 农垦医学, 2008, 30(1): 7-9.
[24] 屈凤莲, 郝学志, 秦叔逵, 刘基巍, 隋广杰, 陈强, 屈涛, 张和平, 孙燕. 亚砷酸注射液治疗原发性肝癌的Ⅱ期多中心临床研究[J]. 中华肿瘤杂志, 2011, 33(9): 697-701.
[25] 郭换珍, 赵直光, 唐中权, 安纪红, 孟江涛, 倪文. 三氧化二砷治疗晚期原发性肝癌的临床观察[J]. 中国肝脏病杂志(电子版), 2014, 6(1): 5-7.
[26] 颜庆余, 南永红, 张建莹. 原发性肝癌应用三氧化二砷治疗的临床研究[J]. 吉林医学, 2009, 30(6): 491-492.
[27] Lu, W., Yang, C., Du, P., Zhang, J.L. and Zhang, J.C. (2017) Effects of Arsenic Trioxide on the Expression of Ezrin in Hepatocellular Carcinoma. Medicine, 96, e7602.
[28] Liu, B., Huang, J.W., Li, Y., Hu, B.S., He, X., Zhao, W., Zheng, Y.B. and Lu, L.G. (2015) Arsenic Trioxide Transarterial Chemoembolization with and without Additional Intravenous Administration of Arsenic Trioxide in Unresectable Hepatocellular Carcinoma with Lung Metastasis: A Single-Blind, Randomized Trial. Journal of Cancer Research and Clinical Oncology, 141, 1103-1108. [Google Scholar] [CrossRef] [PubMed]
[29] 陈宝玲, 饶荣生. 三氧化二砷治疗原发性肝癌的临床及实验研究进展[J]. 实用癌症杂志, 2008, 23(2): 218-220.
[30] 解皓, 李海涛, 吴文娟, 刘保良. 三氧化二砷治疗原发性肝癌的研究进展[J]. 河北医药, 2006, 28(3): 219-220.
[31] 肖鹏, 梅家转, 李瑞君, 白桦, 栗敏, 刘桂举. 三氧化二砷联合经导管动脉化疗栓塞术治疗晚期原发性肝癌的疗效及安全性[J]. 肿瘤基础与临床, 2017, 30(5): 398-400.
[32] 于翔, 李刚, 顾露, 谢坪. 三氧化二砷经导管肝动脉化疗栓塞介入治疗中晚期原发性肝癌临床疗效及安全性观察[J]. 实用医院临床杂志, 2017, 14(2): 49-52.
[33] Wang, H., Liu, Y., Wang, X., Liu, D., Sun, Z., Wang, C., Jin, G., Zhang, B. and Yu, S. (2015) Randomized Clinical Control Study of Locoregional Therapy Com-bined with Arsenic Trioxide for the Treatment of Hepatocellular Carcinoma. Cancer, 121, 2917-2925. [Google Scholar] [CrossRef] [PubMed]
[34] 张新保, 谢建功, 于永忠, 王向日, 徐雨佳, 张和平, 陈莉娟. As2O3经肝动脉介入栓塞治疗原发性肝癌的临床研究[J]. 当代医学, 2010, 16(34): 112-113+132.
[35] 汤日杰, 崔书钟, 潭志明, 王俊, 唐云强, 王家康. 化疗栓塞结合As2O3局部连续灌注治疗肝癌30例临床观察[J]. 中医药导报, 2007, 13(8): 14-15.
[36] 胡琴, 韦永明, 管睿, 宛新安, 王银华, 胡俊. TACE联合三氧化二砷治疗原发性肝癌的临床研究[J]. 现代肿瘤医学, 2014, 22(11): 2679-2681.
[37] Hu, H.T., Yao, Q.J., Meng, Y.L., Li, H.L., Zhang, H., Luo, J.P., Guo, C.Y. and Geng, X. (2017) Arsenic Trioxide Intravenous Infusion Combined with Transcatheter Arterial Chemoembolization for the Treatment of Hepatocellular Carcinoma with Pulmonary Metastasis: Long-Term Outcome Analysis. Journal of Gastroenterology and Hepatology, 32, 295-300. [Google Scholar] [CrossRef] [PubMed]
[38] Lv, X.H., Wang, C.H. and Xie, Y. (2017) Arsenic Trioxide Combined with Transarterial Chemoembolization for Primary Liver Cancer: A Meta-Analysis. Journal of Gastroenterology and Hepatology, 32, 1540-1547. [Google Scholar] [CrossRef] [PubMed]
[39] Song, P., Hai, Y., Ma, W., Zhao, L., Wang, X., Xie, Q., Li, Y., Wu, Z. and Li, H. (2018) Arsenic Trioxide Combined with Transarterial Chemoembolization for Unresectable Primary Hepatic Carcinoma: A Systematic Review and Meta-Analysis. Medicine, 97, e0613. [Google Scholar] [CrossRef] 
[40] 欧东, 陈奕霖, 付斯瑜, 罗德红, 屈天银, 李曾. 三氧化二砷联合TACE治疗中晚期原发性肝癌疗效的Meta分析[J]. 介入放射学杂志, 2018, 27(6): 523-529.
[41] 郑子瑞, 王晓辉, 王晓娟. As2O3联合FuDR、CAP、THP介入治疗中晚期肝癌的疗效对比及意义[J]. 肝脏, 2017, 22(4): 342-344.
[42] 唐鑫, 刘玉宇, 敬方园, 李玉伟. 洛铂联合三氧化二砷TACE治疗老年原发性肝癌的临床疗效观察[J]. 介入放射学杂志, 2017, 26(12): 1136-1139.
[43] Yu, G., Chen, X., Chen, S., Ye, W., Hou, K. and Liang, M. (2015) Arsenic Trioxide Reduces Chemo-Resistance to 5-Fluorouracil and Cisplatin in HBx-HepG2 Cells via Complex Mechanisms. Cancer Cell International, 15, 116. [Google Scholar] [CrossRef] [PubMed]