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邓哲,欧阳昭广,胡玉星,冯婷,陈铮甲,宁迪敏,张博宇,雷宜晨,刘华,田雪飞.薯蓣丸调控HIF-1α与p53表达改善线粒体损伤治疗肝细胞癌的实验研究[J].湖南中医药大学学报英文版,2021,41(7):1010-1016.[Click to copy
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| 薯蓣丸调控HIF-1α与p53表达改善线粒体损伤治疗肝细胞癌的实验研究 |
| 邓哲,欧阳昭广,胡玉星,冯婷,陈铮甲,宁迪敏,张博宇,雷宜晨,刘华,田雪飞 |
| (湖南中医药大学中西医结合学院, 湖南 长沙 410208;湖南中医药大学方证转化湖南省重点实验室, 湖南 长沙 410208;广州医科大学附属口腔医院口腔预防科, 广东 广州 510182;湖南中医药大学第一附属医院, 湖南 长沙 410208;湖南中医药大学针灸推拿学院, 湖南 长沙 410208) |
| 摘要: |
| 目的 观察薯蓣丸对肿瘤微环境中HIF-1α与p53的表达以及线粒体损伤的影响，及其对肝细胞癌的治疗作用。方法 制备人肝癌裸鼠皮下移植瘤模型，雄性BALB/c裸鼠（n=24，5周龄），随机分为4组，每组6只：模型组（0.9%生理盐水0.2 mL/d）、薯蓣丸组（薯蓣丸0.4 g/d），薯蓣丸+顺铂组（薯蓣丸0.4 g/d+每周腹腔注射顺铂5 mg/kg）、顺铂组（每周腹腔注射顺铂5 mg/kg）。每只裸鼠灌胃剂量为0.2 mL/d，每2天测量1次肿瘤体积与小鼠体质量，连续干预14 d后脱颈处死，剥离皮下移植瘤；电镜下观察肿瘤组织线粒体结构和数量；Western blot与RT-qPCR法分别检测人肝癌裸鼠皮下移植瘤中HIF-1α、p53的蛋白及mRNA表达。结果 与模型组相比，薯蓣丸组可抑制人肝癌裸鼠皮下移植瘤的生长，抑制HIF-1α的mRNA与蛋白表达（P<0.05），上调抑癌基因p53的mRNA与蛋白表达（P<0.05），同时改善线粒体结构损伤；与薯蓣丸组或顺铂组相比，薯蓣丸联合顺铂组对HIF-1α、p53基因表达及改善线粒体结构作用更显著（P<0.05）。结论 薯蓣丸可通过促使HIF-1α的失活与p53的活化，改善线粒体结构损伤，从而抑制人肝癌裸鼠皮下移植瘤的生长，与顺铂联用后具有协同增效作用。 |
| 关键词: 肝癌 肿瘤微环境 薯蓣丸 线粒体损伤 HIF-α p53 |
| DOI：10.3969/j.issn.1674-070X.2021.07.007 |
| Received:March 28, 2021 |
| 基金项目:区域创新联合国家自然科学基金重点项目（U20A20408）；国家自然科学基金项目（82074450）；湖南省自然科学基金项目（2020JJ4066）；中西医结合一流学科开放基金项目（2020ZXIJH35，2018ZXJH28）；湖南中医药大学“一方”研究生创新课题（YF201903）；湖南省科技创新人才计划大学生创新创业资助项目（肿瘤外治古膏方系列产品研发与推广运用）；2018年度湖南省大学生创新创业训练计划项目（大黄抗蜈蚣所致肝损伤的“给邪出路”作用及机制研究）。 |
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| Shuyu Pills Improves Mitochondrial Damage by Regulating the Expression of HIF-1α and p53 to Prevent Hepatocellular Carcinoma |
| DENG Zhe,OUYANG Zhaoguang,HU Yuxing,FENG Ting,CHEN Zhengjia,NING Dimin,ZHANG Boyu,LEI Yichen,LIU Hua,TIAN Xuefei |
| (College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Key Laboratory of Translational Research in Formulas and Zheng of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Department of Preventive Dentistry, Stomatological Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong 510182, China;The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Department of Acupuncture and Massage, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To evaluate the effect of Shuyu Pills on the expression of HIF-1α and p53 in tumor microenvironment and mitochondrial damage, and therapeutic effect on treating hepatocellular carcinoma (HCC). Methods The subcutaneously transplanted tumor model of human hepatocellular carcinoma in nude mice was prepared. Male BALB/c nude mice (n=24, 5 weeks old) were randomly divided into 4 groups with 6 mice in each group:model group (administered normal saline, 0.2 mL/d), SYP group (0.4 g/d Shuyu Pills), SYP+DDP group (0.4 g/d Shuyu Pills + weekly intraperitoneal dose of 5 mg/kg cisplatin), DDP group (weekly intraperitoneal dose of 5 mg/kg cisplatin). Each mouse was taken 0.2 mL drug via gavage every day. The tumor volume and body weight of mouse were measured every 2 days. After continuous intervention for 14 days, all the mice were sacrificed by neck removal and subcutaneous graft tumor was removed; the structure and quantity of mitochondria in tumor tissues were observed by electron microscopy; the protein and mRNA expression levels of HIF-1α and p53 of tumor were detected by Western blot and RT-qPCR. Results Compared with model group, SYP group inhibited the growth of subcutaneous transplanted tumor of HCC in nude mice, inhibited the mRNA and protein expression of HIF-1α (P<0.05), upregulated the mRNA and protein expression of tumor suppressor gene p53 (P<0.05), and improved the mitochondrial structure damage; compared with SYP group or DDP group, SYP+DDP group improved the expression of HIF-1α and p53 genes and mitochondrial structure significantly (P<0.05). Conclusion Shuyu Pills could inhibit the growth of subcutaneously transplanted human HCC in nude mice, which might inactivate HIF-1α and activate p53, to improve mitochondrial structural damage, combined with cisplatin, Shuyu Pills has synergistic effect. |
| Key words: hepatocellular carcinoma tumor microenvironment Shuyu Pills mitochondrial damage HIF-1α p53 |
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