人参皂苷Rg3联合GP对Lewis肺癌小鼠抗肿瘤作用  

Anti-tumor Effect of Ginsenoside Rg3 Combined with GP on Lewis Lung Cancer in Mouse

作　　者：王柯 陈函[1,2,3] 胡志强 马康 汪静 WANG Ke;CHEN Han;HU Zhiqiang;MA Kang;WANG Jing(Department of Pharmacology,Ningxia Medical University,Yinchuan 750004,China;Ningxia Collaborative Innovation Center of Regional Characteristic Traditional Chinese Medicine,Yinchuan 750004,China;Key Laboratory of Ningxia Ethnomedicine Modernization,Ministry ofEducation,Yinchuan 750004,China;Oncology Hospital,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学药学院,银川750004 [2]宁夏特色中医药协同创新中心,银川750004 [3]宁夏少数民族医药现代化教育部重点实验室,银川750004 [4]宁夏医科大学总医院肿瘤医院,银川750004

出　　处：《宁夏医科大学学报》2022年第4期343-348,共6页Journal of Ningxia Medical University

基　　金：宁夏回族自治区重点研发计划一般项目(2019BEG03040)。

摘　　要：目的观察人参皂苷Rg3联合GP(吉西他滨联合顺铂)对Lewis肺癌小鼠抗肿瘤作用。方法建立Lewis肺癌小鼠移植瘤模型,评估人参皂苷Rg3联合GP的抗肿瘤作用;组织学切片法检测荷瘤小鼠肝、肾、脾和肿瘤的病理变化;免疫组化法检测肿瘤内微血管密度(MVD)、瘤体血小板表面活化标记物(CD62P)和Nrf2信号通路关键蛋白的表达。结果给药后,与对照组比较,GP组和联合组小鼠肿瘤质量均减轻(P均<0.05)。联合组小鼠的抑瘤率达84.4%,GP组为79.7%,人参皂苷Rg3组为22.8%;组织病理学变化结果显示,人参皂苷Rg3可以促进肿瘤细胞凋亡,并且对GP所致的肝、肾、脾的损伤具有改善作用。GP组小鼠给药后体质量持续下降;联合组小鼠体质量呈先下降后增加趋势。免疫组化结果显示,对照组小鼠肿瘤组织微血管大量增生,而人参皂苷Rg3组、GP组和联合组小鼠肿瘤MVD均较对照组减少(P均<0.05);与对照组相比,各治疗组CD62P蛋白表达均出现不同程度降低(P均<0.05);并且人参皂苷Rg3联合GP化疗可下调Nrf2信号通路蛋白(Nrf2、NQO1、GSTA1与HO-1)的表达。结论人参皂苷Rg3与GP联用后可增强其对Lewis肺癌小鼠肿瘤生长及肿瘤新生血管生成的抑制作用,其抑瘤作用可能与干预Nrf2信号通路和CD62P的表达相关;且人参皂苷Rg3与GP联用后可起到增效减毒作用。Objective To observe the anti-tumor effect of Ginsenoside Rg3 combined with GP(gemcitabine and cisplatin)on Lewis lung cancer bearing mice.Methods Lewis lung cancer model in mice was established to evaluate the anti-tumor effect of Ginsenoside Rg3 combined with GP.The pathological changes of liver,kidney,spleen and tumor were detected by histological section technology.The expression of microvascular density(MVD),CD62P and key proteins of Nrf2 signaling pathway were detected by immunohistochemistry.Results After administration,compared with the control group,the tumor weight of GP group and combination group was significantly lower(P all<0.05).In terms of tumor inhibition rate was 84.4%,79.7%and 22.8%in the combination group,the GP group and the Ginsenoside Rg3 group,respectively.Moreover,the results of histopathological changes showed that Ginsenoside Rg3 could promote tumor cells apoptosis and improve the damage of liver,kidney and spleen caused by GP.In terms of body weight,it continued to decrease after administration in the GP group and the body weight of the mice in combination group showed a trend of decreasing firstly and then increasing.The results of immunohistochemistry showed that microvessels were greatly proliferated in the tumor tissues of the control mice,while MVD was significantly reduced(P all<0.05)in Ginsenoside Rg3 group,GP group and combination group compared.The protein expression of CD62P in each treatment group appeared to be decreased to various degrees(P all<0.05).And Ginsenoside Rg3 combined with GP could decrease the protein expression of Nrf2 signaling pathway(Nrf2,NQO1,GSTA1 and HO-1).Conclusion Ginsenoside Rg3 combined with GP enhanced effect of inhibiting tumor growth and angiogenesis in Lewis lung cancer mice.And its tumor suppressive effect may be associated with intervening Nrf2 signaling pathway and CD62P expression.Moreover,Ginsenoside Rg3 combined with GP chemotherapy could exert a synergistic and attenuating effect in tumor treatment.

关 键 词：人参皂苷RG3 吉西他滨联合顺铂 LEWIS肺癌 Nrf2信号通路 增效减毒 

分 类 号：R734.2[医药卫生—肿瘤]