金雀异黄素协同三氧化二砷共同抑制人体肝癌细胞_蒋永池 - 金转停_金雀异黄素Genistein

针对病种：肝癌

发表时间：2010年3月

发表国家：英国

登载刊物：癌症科学

研究单位：中国哈尔滨医科大学第一附属医院脾外科中心一般手术部;新西兰奥克兰大学分子医学和病理学系、医学系和健康科学系

研究人员：蒋永池，马勇，陈晓宁等

主要结论：金雀异黄素协同 ATO可以减少细胞的生命力，诱导细胞凋亡，并且降低细胞的 ΔΨm。金雀异黄素结合 ATO被充分证明可以作为抗击肝癌的治疗方法，并且没有毒副作用.

Cancer Science, 2010, 101(4):975–983.

Genistein synergizes with arsenic trioxide to suppress human hepatocellular carcinoma

Hongchi Jiang, Yong Ma, Xiaoning Chen, et al

Department of General Surgery, The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

Arsenic trioxide (ATO) is of limited therapeutic benefit for the treatment of solid tumors. Genistein exhibits anticancer and pro-oxidant activities, making it a potential candidate to enhance the efficacy of ATO whose cytotoxicity is oxidation-sensitive. This study sought to determine whether genistein synergizes with ATO to combat hepatocellular carcinoma (HCC). Three human HCC cell lines, namely HepG2, Hep3B, and SK-Hep-1, were incubated with ATO, genistein, or ATO + genistein. The cells were also pretreated with antioxidant agents N-acetyl-L-cysteine (NAC) or butylated hydroxyanisole (BHA). Cell viability, apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨ_m), expression of Bcl-2, Bax, caspase-9, and -3, and release of cytochrome c into the cytosol were examined. The synergistic effect of ATO and genistein was also assessed using HepG2 xenografts subcutaneously established in BALB/c nude mice. The results show that genistein synergized with ATO to reduce viability, induce apoptosis, and diminish the ΔΨ_m of cells. The combination therapy down-regulated Bcl-2 expression, up-regulated Bax expression, enhanced the activation of caspase-9 and -3, and increased the release of cytochrome c. The synergistic effect of ATO and genistein was diminished by pretreatment with NAC or BHA. Genistein increased the production of intracellular ROS, while ATO had little effect. Genistein synergized with a low dose of ATO (2.5 mg/kg) to significantly inhibit the growth of HepG2 tumors, and suppress cell proliferation and induce apoptosis in situ. There were no obvious side effects, as seen with a high dose of ATO (5 mg/kg). Combining genistein with ATO warrants investigation as a therapeutic strategy to combat HCC.

英国《癌症科学》2010年3月

金雀异黄素协同三氧化二砷共同抑制人体肝癌细胞

蒋永池，马勇，陈晓宁等

中国哈尔滨医科大学第一附属医院脾外科中心一般手术部;新西兰奥克兰大学分子医学和病理学系、医学系和健康科学系

三氧化二砷 (ATO) 治疗实体瘤的作用比较有限。金雀异黄素展现出抗癌和助氧化活性，可以作为潜在的药物来增强细胞毒性氧化敏感的 ATO 的疗效。本研究旨在确定金雀异黄素能否与 ATO协同对抗肝细胞癌 (HCC)。在ATO、金雀异黄素，或 ATO + 金雀异黄素中分别孵育三种人体肝癌细胞株， HepG2，Hep3B 和 SK-Hep-1。这些细胞先用抗氧化剂 N-乙酰-L-半胱氨酸 (NAC) 或丁羟基苯甲醚 (BHA) 预处理。细胞的生存，凋亡，细胞内活性氧簇 (ROS)，线粒体膜电位 (ΔΨm)，Bcl-2、 Bax，半胱氨酸蛋白酶-9和-3的表达，以及细胞色素 c到细胞质的释放均被考察。使用在BALB/c 裸小鼠皮下移植的HepG2 裸鼠移植瘤来评估 ATO 和金雀异黄素的协同作用。结果表明，金雀异黄素协同 ATO可以减少细胞的生命力，诱导细胞凋亡，并且降低细胞的 ΔΨ_m。这种联合疗法可以下调 Bcl-2的表达，上调 Bax 的表达，增强半胱氨酸蛋白酶-9 和-3的活性，并且增加细胞色素 c 的释放。当细胞被NAC或者BHA预处理后ATO 和染料木素的协同作用会降低。金雀异黄素促进了细胞内 ROS 的产生而ATO 的影响很小。金雀异黄素与低剂量的 ATO （2.5 mg/kg）会明显抑制 HepG2 肿瘤的生长，抑制细胞增殖并且原位诱导细胞凋亡。当使用高剂量的 ATO （5 mg/kg）也没有明显的毒副作用。金雀异黄素结合 ATO被充分证明可以作为抗击肝癌的治疗方法。