浏览全部资源
扫码关注微信
1.三峡大学 健康医学院,湖北 宜昌 433000
2.三峡大学 国家中药药理(肿瘤)三级实验室,湖北 宜昌 433000
3.三峡大学 基础医学院,湖北 宜昌 433000
Published:05 March 2023,
Published Online:24 November 2022,
Received:08 August 2022,
扫 描 看 全 文
蒯晴叶,程叶,张艳等.华蟾素抗消化道恶性肿瘤及其作用机制研究进展[J].中国实验方剂学杂志,2023,29(05):264-271.
KUAI Qingye,CHENG Ye,ZHANG Yan,et al.Effect and Mechanism of Cinobufotalin Against Gastrointestinal Malignant Tumors: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):264-271.
蒯晴叶,程叶,张艳等.华蟾素抗消化道恶性肿瘤及其作用机制研究进展[J].中国实验方剂学杂志,2023,29(05):264-271. DOI: 10.13422/j.cnki.syfjx.20230127.
KUAI Qingye,CHENG Ye,ZHANG Yan,et al.Effect and Mechanism of Cinobufotalin Against Gastrointestinal Malignant Tumors: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):264-271. DOI: 10.13422/j.cnki.syfjx.20230127.
从全球范围来看,中国是消化道疾病较为流行的国家,其中以消化道肿瘤为著,主要包括肝癌、胰腺癌、结直肠癌等。消化道肿瘤新发病例数与死亡例数均占全球癌症前10位,且肿瘤疾病发生率与死亡率呈逐年增长趋势,因此肿瘤的预防与治疗显得尤为重要。随着中药在医学界的推广应用及分子生物学和药理学的迅速发展,越来越多的中药潜在活性成分被提取出来并经研究证实,其以多靶点、多通路的原理有效地抑制肿瘤细胞,发挥中药抗肿瘤作用。华蟾素是源于中华蟾蜍的皮经提取分离得到的有效组分,临床上被制成多种剂型,并具有抗肿瘤、调节免疫、强心升压、镇痛、抗炎消肿等作用。现代临床多用于肝癌、肺癌、结直肠癌、胃癌等恶性肿瘤的治疗,改善中晚期患者的不良反应,提高患者生活质量及5年生存率。分子机制研究表明华蟾素可通过诱导细胞凋亡、调控细胞周期抑制细胞增殖、抑制血管生成、调节免疫应答、逆转多药耐药和放化疗增敏、抑制肿瘤炎症及侵袭转移等多种途径发挥疗效。该综述着重于强调近年来在国内外相关研究中对华蟾素抗消化道肿瘤疾病的临床应用与机制,为华蟾素抗肿瘤研究提供理论依据,推进华蟾素辅助或临床联合治疗手段,为药物的再次开发与研究应用提供参考条件。
Digestive tract diseases, especially digestive tract tumors, including liver cancer, pancreatic cancer, and colorectal cancer, have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world, and the incidence and mortality of tumor diseases have been increasing year by year. Therefore, the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology, more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor, immunomodulatory, cardiac boosting, pain-easing, anti-inflammatory, and swelling-relieving activities. In clinical practice, cinobufotalin is mainly used to assist the treatment of liver cancer, lung cancer, colorectal cancer, gastric cancer and other malignant tumors, which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis, regulating cell cycle, inhibiting cell proliferation and angiogenesis, modulating immune response, reversing multidrug resistance, enhancing radiochemotherapy sensitivity, inhibiting tumor inflammation, invasion, and metastasis, etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years, aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin, promote the application of cinobufotalin in tumor treatment, and facilitate the further research and development of this compound.
消化道肿瘤华蟾素抗肿瘤作用临床应用综述
digestive tract tumorcinobufotalinanti-tumor effectclinical applicationreview
刘宗超, 李哲轩, 张阳, 等. 2020全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2021,7(2):1-14.
GONZALEZ R S, RAZA A, PROPST R, et al. Recent advances in digestive tract tumors: Updates from the 5th Edition of the World Health Organization "Blue book"[J]. Arch Pathol Lab Med, 2021,145(5):607-626.
韩玲玉. 华蟾素中蟾毒配基类成分化学、代谢、活性及毒性的研究[D]. 北京:中国中医科学院, 2018.
REN J, WANG S, JIN L, et al. Cinobufagin inhibits tumor growth by inducing apoptosis through Notch signaling pathways in human cholangiocarcinoma[J]. Transl Cancer Res, 2019,8(6):2461-2469.
QIN T J, ZHAO X H, YUN J, et al. Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinoma[J]. World J Gastroenterol, 2008,14(33):5210-5216.
袁福建, 赖小强, 黄少鹏. 华蟾素胶囊联合介入治疗肝癌临床疗效观察[J]. 实用中西医结合临床, 2021,21(16):83-84.
YANG Z, LUO H, WANG H, et al. Preparative isolation of bufalin and cinobufagin from Chinese traditional medicine Chansu[J]. J Chromatogr Sci, 2008,46(1):81-85.
LI F J, HU J H, REN X, et al. Toad venom: A comprehensive review of chemical constituents, anticancer activities, and mechanisms[J]. Arch Pharm (Weinheim), 2021,354(7):e2100060.
吴欢, 唐卯星, 陶欣怡, 等. UPLC-ESI-QTOF/MS~E结合UNIFI快速分析华蟾素注射液化学成分[J]. 天然产物研究与开发, 2020,32(3):498-506.
曹毛毛, 李贺, 孙殿钦, 等. 全球肝癌2020年流行病学现状[J]. 中华肿瘤防治杂志, 2022,29(5):322-328.
JIN X, WANG J, ZOU S, et al. Cinobufagin triggers defects in spindle formation and cap-dependent translation in liver cancer cells by inhibiting the AURKA-mTOR-eIF4E axis[J]. Am J Chin Med, 2020,48(3):651-678.
LI W, PEI S, ZHANG X, et al. Cinobufotalin inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells through down-regulate β-catenin in vitro and in vivo[J]. Eur J Pharmacol, 2022, doi:10.1016/j.ejphar.2022.174886http://dx.doi.org/10.1016/j.ejphar.2022.174886.
袁贤达, 王骏, 金明吉, 等. 华蟾素油剂对肝癌细胞的体内外抑制活性及肿瘤微环境中对免疫细胞的影响[J]. 世界中西医结合杂志, 2019,14(12):1629-1637.
王培培, 王永辉, 王丽森, 等. 华蟾素辅助顺铂化疗对H22肝癌小鼠的抑瘤作用及其相关机制研究[J]. 中国中药杂志, 2020,45(16):3945-3951.
魏晓露, 杨健, 司南, 等. 华蟾素蟾毒配基类有效组分体内免疫效果分析[J]. 中国实验方剂学杂志, 2016,22(21):87-92.
朱晓燕, 孟志强, 陈震, 等. 华蟾素注射剂对荷人胰腺癌细胞株SW1990裸小鼠的抑瘤作用[J]. 中国临床药学杂志, 2013,22(5):290-293.
周杰. 基于miR-21对胰腺星状细胞EMT的影响探讨华蟾素改善胰腺癌微环境的机制[D]. 北京:北京中医药大学, 2020.
潘阳, 邵淑丽, 冯元, 等. 华蟾素诱导人胃癌MGC-803细胞凋亡[J]. 基因组学与应用生物学, 2021,40(Z2):2819-2824.
李珊珊, 邵淑丽, 冯元, 等. 华蟾素诱导人胃癌MKN-45细胞凋亡[J]. 基因组学与应用生物学, 2021,40(4):1846-1851.
徐咏梅, 刘声. 华蟾素胶囊联合化疗对中晚期胃癌的疗效观察[J]. 世界中医药, 2016,11(7):1212-1214.
LONG Y, WANG Z, FAN J, et al. A hybrid membrane coating nanodrug system against gastric cancer via the VEGFR2/STAT3 signaling pathway[J]. J Mater Chem B, 2021,9(18):3838-3855.
蔡红妃, 求是. 华蟾素注射液联合化疗治疗老年结直肠癌患者近期疗效观察及对患者血清肿瘤标志物和免疫功能的影响[J]. 中国医师进修杂志, 2020(4):368-369.
BAI Y, WANG X, CAI M, et al. Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition[J]. Am J Cancer Res, 2021,11(1):200-214.
LI X, CHEN C, DAI Y, et al. Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia-inducible factor 1α axis[J]. Cancer Sci, 2019,110(5):1724-1734.
YUAN Z T, SHI X J, YUAN Y X, et al. Bufalin reverses ABCB1-mediated drug resistance in colorectal cancer[J]. Oncotarget, 2017,8(29):48012-48026.
REN F, SHEN J, SHI H, et al. Novel mechanisms and approaches to overcome multidrug resistance in the treatment of ovarian cancer[J]. Biochim Biophys Acta, 2016,1866(2):266-275.
LU X S, QIAO Y B, LI Y, et al. Preclinical study of cinobufagin as a promising anti-colorectal cancer agent[J]. Oncotarget, 2017,8(1):988-998.
DENG X, SHENG J, LIU H, et al. Cinobufagin promotes cell cycle arrest and apoptosis to block human esophageal squamous cell carcinoma cells growth via the p73 signalling pathway[J]. Biol Pharm Bull, 2019,42(9):1500-1509.
胡金凤, 张东伟, 夏黎明. 华蟾素治疗中晚期胆囊癌47例临床研究[J]. 中医药临床杂志, 2016,28(1):72-75.
QI F, INAGAKI Y, GAO B, et al. Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas- and mitochondria-mediated pathways[J]. Cancer Sci, 2011,102(5):951-958.
李俊杰, 邬海峰, 张东明, 等. 华蟾素体外抑制胆囊癌GBC-SD细胞增殖与侵袭的机制研究[J]. 中国当代医药, 2021,28(31):27-32.
JIA J, LI J, ZHENG Q, LI D. A research update on the antitumor effects of active components of Chinese medicine ChanSu[J]. Front Oncol, 2022, doi: 10.3389/fonc.2022.1014637http://dx.doi.org/10.3389/fonc.2022.1014637.
ZHAO L, FU L, XU Z, et al. The anticancer effects of cinobufagin on hepatocellular carcinoma Huh7 cells are associated with activation of the p73 signaling pathway[J]. Mol Med Rep, 2019,19(5):4119-4128.
YANG A L, WU Q, HU Z D, et al. A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling[J]. Toxicol Appl Pharmacol, 2021, doi:10.1016/j.taap.2021.115739http://dx.doi.org/10.1016/j.taap.2021.115739.
YANG A, WU Q, CHEN Q, et al. Cinobufagin restrains the growth and triggers DNA damage of human hepatocellular carcinoma cells via proteasome-dependent degradation of thymidylate synthase[J]. Chem Biol Interact, 2022, doi:10.1016/j.cbi.2022.109938http://dx.doi.org/10.1016/j.cbi.2022.109938.
NI T, WANG H, LI D, et al. Huachansu capsule inhibits the proliferation of human gastric cancer cells via Akt/mTOR pathway[J]. Biomed Pharmacother, 2019, doi:10.1016/j.biopha.2019.109241http://dx.doi.org/10.1016/j.biopha.2019.109241
BAEK S H, KIM C, LEE J H, et al. Cinobufagin exerts anti-proliferative and pro-apoptotic effects through the modulation ROS-mediated MAPKs signaling pathway[J]. Immunopharmacol Immunotoxicol, 2015,37(3):265-273.
ENGELAND K. Cell cycle arrest through indirect transcriptional repression by p53: I have a dream[J]. Cell Death Differ, 2018,25(1):114-132.
WU Q, LIN W D, LIAO G Q, et al. Antiproliferative effects of cinobufacini on human hepatocellular carcinoma HepG2 cells detected by atomic force microscopy[J]. World J Gastroenterol, 2015,21(3):854-861.
张振玉,张昆和,王崇文,等. 华蟾素对三种消化系肿瘤细胞杀伤机制研究[J]. 中药药理与临床, 1999(5):28-29.
胡叶. 华蟾素注射液腹腔灌注干预结肠癌血性腹水中VEGF表达的机制研究[D]. 北京:北京中医药大学, 2018.
崔永欣, 连加玉. 华蟾素胶囊对结直肠癌术后辅助化疗患者免疫功能及术后复发的影响[J]. 中国合理用药探索, 2022,19(1):102-107.
孙志刚,李佳,焦勤书,等.动脉置管灌注华蟾素注射液联合索拉非尼治疗经动脉化疗栓塞术后原发性肝癌患者近期疗效观察[J].中华中医药学刊,2022,40(5):223-226.
YU Y, WANG H, MENG X, et al. Immunomodulatory effects of cinobufagin on murine lymphocytes and macrophages[J]. Evid Based Complement Alternat Med, 2015,doi:10.1155/2015/835263http://dx.doi.org/10.1155/2015/835263
吴晋周, 唐纪全. 华蟾素注射液联合FOLFOX4治疗胃癌患者癌性疼痛的临床效果[J]. 临床医学研究与实践, 2020,5(33):18-20.
杨兴肖, 马鸣, 单保恩, 等. 华蟾素注射液对人食管癌细胞增殖、侵袭和化疗敏感性的影响及其机制[J]. 癌变·畸变·突变, 2017,29(2):96-101.
韦艳, 卢珩, 王荣荣, 等. 华蟾素注射液抗肝癌细胞多药耐药性的蛋白质组学分析[J]. 基础医学与临床, 2014,34(6):814-818.
高雁, 侯坤. 晚期胰腺癌患者应用华蟾素胶囊辅助放疗的效果分析[J]. 慢性病学杂志, 2021,22(10):1616-1618.
李时超, 殷佩浩, 陈腾, 等. 华蟾素对溃疡性结肠炎大鼠的作用及机制[J]. 中国临床药理学杂志, 2021,37(21):2924-2928.
LILI W, YANG H, XIANBIAO X, et al. Anti-inflammatory and antinociceptive activities of bufalin in rodents[J]. Med Inflam, 2014, doi:10.1155/2014/171839http://dx.doi.org/10.1155/2014/171839.
杨建波, 刘鹏, 张文兴, 等. 华蟾素通过IGF-1R信号通路对肝癌细胞增殖、迁移及侵袭的影响[J]. 中医学报, 2021,36(12):2636-2641.
刘娟, 李春霞, 马海琳, 等. 华蟾素辅助顺铂化疗肝癌移植瘤小鼠的抑瘤作用及对肠道菌群、外周血淋巴细胞亚型的影响[J]. 临床和实验医学杂志, 2021,20(21):2249-2252.
赖桂花,王菲,聂多锐,等.骨转移癌痛发病机制及中医药防治研究进展[J].中国实验方剂学杂志,2022,doi:10.13422/j.cnki.syfjx.202202026http://dx.doi.org/10.13422/j.cnki.syfjx.202202026.
马丁丁, 戴少楚, 王志. 华蟾素胶囊 多西他赛 奥沙利铂及替吉奥方案治疗晚期胃癌临床疗效分析[J]. 基层医学论坛, 2021,25(16):2267-2268.
杨庆伟, 彭世龙. XELOX方案联合华蟾素胶囊治疗晚期结直肠癌的临床效果及安全性[J]. 临床医学研究与实践, 2021,6(12):36-38.
李璐, 黄艳洁, 郑纪宁. 华蟾素联合化疗治疗结直肠癌的疗效与安全性的系统评价[J]. 承德医学院学报, 2022,39(2):91-95.
杨浩,马龙安,李汾,刘爱琴. 华蟾素联合药物灌注治疗晚期胆管癌19例疗效分析[J]. 现代肿瘤医学, 2003(3):203-204.
牛顺海. 华蟾素注射液联合吉西他滨治疗晚期胰腺癌疗效观察[J]. 临床合理用药杂志, 2014,7(11):61-62.
章秀梅, 陆绍华, 马翔, 等. 华蟾素注射液联合西妥昔单抗佐治胸段食管癌淋巴结转移临床研究[J]. 浙江中医杂志, 2019,54(9):629-630.
杨小飞, 张鹏飞. 华蟾素胶囊联合羟基喜树碱对中晚期食管癌疼痛患者的疗效分析[J]. 现代医学, 2019,47(11):1333-1336.
唐朝锋. 华蟾素胶囊联合XELOX化疗方案治疗老年晚期食管癌患者的效果[J]. 河南医学研究, 2019,28(4):718-720.
闫兵杰, 韩娜娜. 华蟾素胶囊联合放化疗对晚期食管癌的临床效果[J]. 河南医学研究, 2020,29(2):270-272.
张明, 杨星辰, 金丽, 等. 122例中药制剂所致ADR特点及其影响因素[J]. 中成药, 2021,43(8):2268-2271.
曹赛勇, 任伟芳, 方忠宏, 等. 华蟾素胶囊致药物性肝损伤1例[J]. 中国现代应用药学, 2022,39(4):542-543.
0
Views
21
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution