参芪健胃颗粒调节能量代谢重编程抑制胃癌作用及机制  

Effect and Mechanism of Shenqi Jianwei(参芪健胃)Granules on Inhibiting Gastric Cancer Growth by Modulating Energy Metabolism Reprogramming

作　　者：余明珠 潘巧岭 李文标 杜婷婷 吴辉[1] 黄菲[1] 吴晓俊[1] 石海莲[1] YU Mingzhu;PAN Qiaoling;LI Wenbiao;DU Tingting;WU Hui;HUANG Fei;WU Xiaojun;SHI Hailian(Shanghai Key Laboratory of Compound Chinese Medicines,the Ministry of Education(MOE)Key Laboratory for Standardization of Chinese Medicines,the SATCM Key Laboratory for New Resources&Quality Evaluation of Chinese Medicine,Research Center of Shanghai Traditional Chinese Medicine Standardization,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203)

机构地区：[1]上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所,上海201203

出　　处：《中药药理与临床》2023年第11期24-29,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：上海市自然科学基金(编号:21ZR1462800、23ZR1463100);国家自然科学基金项目(编号:81603354);研究生创新培养专项(编号:Y2021088);上海市复方中药重点实验室开放课题(编号:21DZ2270500)。

摘　　要：目的:探究参芪健胃颗粒对胃癌细胞能量代谢的影响及其可能的分子机制。方法:裸鼠皮下注射胃癌细胞MGC803制备裸鼠胃癌细胞皮下移植瘤模型,随机分为模型对照组、5-氟尿嘧啶(5-FU)50 mg/kg组、参芪健胃颗粒960 mg/kg组,各组灌胃或腹腔注射给予相应药物或生理盐水,每3 d相同时间测量肿瘤大小及裸鼠体质量,给药21 d后处理动物,剥离肿瘤并称质量;HE染色法检测参芪健胃颗粒对裸鼠胃癌细胞皮下移植瘤组织病理改变的影响;TUNEL法检测参芪健胃颗粒对裸鼠胃癌细胞皮下移植瘤组织细胞凋亡的影响;Western blot法检测参芪健胃颗粒对裸鼠胃癌细胞皮下移植瘤组织凋亡、能量代谢相关蛋白表达的影响。结果:与模型对照组相比,参芪健胃颗粒960 mg/kg组显著抑制裸鼠胃癌细胞皮下移植瘤的生长,显著改善移植瘤组织的病理,促进移植瘤组织细胞的凋亡(P<0.01),明显下调移植瘤组织糖酵解相关蛋白磷酸化丙酮酸脱氢酶α1(p-PDHA1)、丙酮酸脱氢酶激酶1(PDHK1)和乳酸脱氢酶(LDHA)的蛋白表达(P<0.05或P<0.01),显著降低移植瘤组织B细胞淋巴瘤-2(BCL-2)/Bcl-2相关X蛋白(BAX)的蛋白表达比例(P<0.01),上调切割型半胱氨酸-天冬氨酸蛋白酶3(Cleaved caspase-3)和Cleaved caspase-9的蛋白表达,显著抑制移植瘤组织c-Myc和低氧诱导因子1α(HIF-1α)的蛋白表达(P<0.01)。结论:参芪健胃颗粒可能通过抑制HIF-1α和c-Myc表达,调控能量代谢重编程相关蛋白和促凋亡相关蛋白的表达,从而促进细胞凋亡,最终抑制胃癌的生长。Objective:To explore the effect of Shenqi Jianwei(参芪健胃)Granules on the energy metabolism of gastric cancer cells and its possible molecular mechanism.Methods:The nude mice model of gastric cancer cell subcutaneous transplantation was established by subcutaneous injection of gastric cancer cell MGC803.Mice were randomly divided into the model control group,positive control group(5-FU 50 mg/kg),and Shenqi Jianwei Granule(960 mg/kg)group.Mice in each group were given corresponding drugs or saline water,and then the tumor size and body weight of the nude mice were measured at the same moment every three days.After drug administration for 21 days,the mice were euthanized,and the tumors were isolated and weighed.The pathological changes of tumor tissue of MGC803 cell caused by Shenqi Jianwei Granules were detected by hematoxylin-eosin(HE)staining.The effect of Shenqi Jianwei Granules on apoptosis in tumor tissue of MGC803 cell was detected by deoxynucleotide terminal transferase-mediated nick end labeling(TUNEL)assay.The effect of Shenqi Jianwei Granules on the expression of proteins related to apoptosis and energy metabolism in tumor tissue of MGC803 cell was detected by western blot(WB).Results:Compared with the model control group,Shenqi Jianwei Granule(960 mg/kg)group significantly inhibited tumor growth of nude mice with subcutaneous xenografts of gastric cancer cells,significantly improved the pathology of tumor tissue,and promoted the cell apoptosis in tumor tissue(P<0.01).It also significantly down-regulated protein expression of glycolysis-related proteins phosphorylated pyruvate dehydrogenaseα1(p-PDHA1),pyruvate dehydrogenase kinase 1(PDHK1),and lactate dehydrogenase(LDHA)in tumor tissue(P<0.05 or P<0.01),significantly reduced the ratio of protein expression of B cell lymphoma-2(Bcl-2)/Bcl-2-related X protein(Bax)in tumor tissue(P<0.01),up-regulated the protein expression of Cleaved caspase-3 and Cleaved caspase-9,and significantly inhibited protein expressions of c-Myc and hypoxia-inducible factor 1

关 键 词：参芪健胃颗粒 胃癌 能量代谢重编程 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]