中药复方SC01联合环磷酰胺抑制肝癌肺转移作用及机制研究  

Study on the inhibitory effect and mechanism of traditional Chinese medicine formula SC01combined with cyclophosphamideo n lung metastasis of hepatocellular carcinoma

作　　者：吉胡日布 彭靖兰 李亚南 李慧 王玉娟 代鑫燕 周俊福 严亨秀 JI-HU Ri-bu;PENG Jing-lan;LI Ya-nan;LI Hui;WANG Yu-juan;DAI Xin-yan;ZHOU Jun-fu;YAN Heng-xiu(School of Pharmacy,Southwest Minzu University,Chengdu 610225,China;School of Animal Husbandry and Veterinary Medicine,Southwest Minzu University,Chengdu 610041,China;Qinghai-Tibetan Plateau Research Institute,Southwest Minzu University,Chengdu 610041,China)

机构地区：[1]西南民族大学药学院,四川成都610225 [2]西南民族大学畜牧兽医学院,四川成都610041 [3]西南民族大学青藏高原研究院,四川成都610041

出　　处：《西南民族大学学报（自然科学版）》2023年第2期156-164,共9页Journal of Southwest Minzu University(Natural Science Edition)

基　　金：四川省科技厅应用基础项目(2021YJ0256);西南民族大学中央高校基本科研业务费专项资金优秀学生培养工程项目(2021NYYXS22)。

摘　　要：探讨中药复方SC01联合环磷酰胺(CTX)抑制H22肝癌肺转移的作用及可能机制.在H22肝癌肺转移小鼠建模第二天,用中药复方SC01按高、中、低剂量连续灌胃14 d, CTX腹腔给药14 d,隔天一次.通过HE、免疫组化、流式细胞分析、ELISA、Western Blot等方法研究联合用药对肝癌肺转移的抑制作用及对MDSCs和相关细胞因子的影响.结果显示,联合用药组具有较好的抑制肝癌肺转移的效果,且具有剂量依赖性,表现在显著抑制肺转移结节数,升高小鼠胸腺、脾脏指数,降低肺组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、血管内皮生长因子(vascular endothelial growth factor, VEGF)和白介素-6(inter leukin-6,IL-6)的表达,减少肺脏和血液中髓源性抑制细胞(Myeloid-derived suppressor cells, MDSCs)的募集,降低免疫抑制性细胞因子白介素-10(interleukin-10,IL-10)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)的表达,下调肺组织磷酸化信号转导和转录激活因子3(Phosphorylated signal transducer and activator oftranscription 3,p-STAT3)和磷酸化蛋白激酶B(Phosphorylated protein kinase B,p-AKT)水平.结果表明,中药复方SC01联合CTX对H22肝癌细胞肺转移有明显抑制作用,其机制可能是通过减少IL-6、VEGF、IL-10和TGF-β1的分泌,通过下调AKT/STAT3信号通路调控相关蛋白从而减少MDSCs的产生和募集,改善肿瘤免疫抑制状态.This study aimed to investigate the effect and possible mechanism of traditional Chinese medicine formula SC01 com⁃bined with cyclophosphamide(CTX)in inhibiting lung metastasis of H22 hepatocellular carcinoma.On the second day after model⁃ing of H22 hepatocellular carcinoma with lung metastasis,traditional Chinese medicine formula SC01 was administered by gavage at high,medium and low doses for 14 days,and CTX was administered intraperitoneally once every other day for 14 days.HE,im⁃munohistochemistry,flow cytometry,ELISA and Western Blot were used to analyze the inhibitory effect of the combination on lung metastasis of hepatocellular carcinoma and the effect on MDSCs and related cytokines.The results showed that the combination group had a good inhibitory effect on lung metastasis of hepatocellular carcinoma in a dose⁃dependent manner,which was manifes⁃ted by significantly inhibiting the number of lung metastatic nodules,increasing the index of thymus and spleen in mice,reducing the expression of matrix metalloproteinase⁃9(MMP⁃9),vascular endothelial growth factor(VEGF)and interleukin⁃6(IL⁃6)in lung tissue,and reducing Myeloid⁃derived suppressor in lung and blood cells,MDSCs),reducing the expression of immunosuppressive cytokines interleukin⁃10(IL⁃10)and transforming growth factor⁃β1(TGF⁃β1),down⁃regulating phosphorylation signal transduction and transcriptional activator 3(Phosphorylated signal transducer and),activator of transcription 3,p⁃STAT3)and phosphorylated protein kinase B(p⁃AKT)levels.The results showed that traditional Chinese medicine formula SC01 combined with CTX had a significant inhibitory effect on lung metastasis of H22 hepatoma cells.Its mechanism may be through reducing the secretion of IL⁃6,VEGF,IL⁃10 and TGF⁃β1,down⁃regulating AKT/STAT3 signaling pathway related proteins,thus reducing the production and recruitment of MDSCs,and improving the immunosuppressive state of tumor.

关 键 词：中药复方SC01 肝癌肺转移 免疫抑制 MDSCS 

分 类 号：R96[医药卫生—药理学]