摘要
目的 探讨参芪扶正注射液对肺腺癌顺铂耐药A549/DDP细胞株荷瘤裸鼠移植瘤的抑瘤作用及其对c-Myc调控的肿瘤干性-耐药轴的干预作用。方法 体外培养肺腺癌顺铂耐药细胞株A549/DDP,接种于BALB/c-nu裸鼠腋窝皮下,荷瘤成功后实验动物随机分成5组,对照组及药物干预组,分别给予顺铂、参芪扶正注射液及不同剂量参芪扶正注射液(低、高剂量)联合顺铂干预。检测各组瘤重及抑瘤率;HE染色观察各组肿瘤组织病理形态学改变;透射电镜观察各组肿瘤细胞超微结构变化;免疫组化法和蛋白质印迹法检测移植瘤组织中ABCC1、ALDH1、c-Myc的表达。结果 与对照组相比,药物干预组肿瘤瘤重有不同程度减轻(均P<0.05),其中参芪扶正注射液低、高剂量联合顺铂干预组与顺铂单独干预组相比亦存在统计学差异(P<0.05);HE染色显示,与对照组相比,干预组肿瘤细胞出现凋亡,且坏死灶增加;透射电镜结果显示,参芪扶正注射液低、高剂量联合顺铂干预组较顺铂组细胞损伤更加严重,重度水肿;免疫组化法和蛋白质印迹法显示,顺铂单独干预组肿瘤组织c-Myc表达上调,而不同剂量参芪扶正注射液联合顺铂组均可显著下调移植瘤ABCC1、ALDH1、c-Myc的表达(P<0.05)。结论 参芪扶正注射液联合顺铂具有下调ABCC1、ALDH1、c-Myc的表达,抑制c-Myc调控的肿瘤干性-耐药轴提高肺腺癌耐药细胞顺铂敏感性的作用。
Objective To investigate the antitumor effect of Shenqi Fuzheng Injection(参芪扶正注射液)on cisplatin-resistant A549/DDP cell line xenografts in nude mice and its intervention on tumor stemness-resistance axis regulated by c-Myc.Methods The cisplatin-resistant lung adenocarcinoma cell line A549/DDP was cultured in vitro and inoculated into the axillary subcutaneous of BALB/c-nu nude mice.After successful tumor loading,the experimental animals were randomly divided into five groups,the control group and the drug intervention groups were given cisplatin,Shenqi Fuzheng Injection,and different doses of Shenqi Fuzheng Injection(low and high doses)combined with cisplatin intervention,respectively.The tumor weight and tumor inhibition rate were detected in each group.HE staining was used to observe the pathomorphological changes of tumor tissues in each group.The ultrastructural changes of tumor cells in each group were observed by transmission electron microscope.The expressions of ABCC1,ALDH1 and c-Myc in the xenografts tissue were detected by immunohistochemistry method and western blot.Results Compared with that in the control group,the tumor weight was reduced to different extents in the medication intervention groups(all P<0.05).The tumor weights of the low and high doses of Shenqi Fuzheng Injection combined with cisplatin intervention groups were also significantly different from that in the cisplatin alone intervention group(P<0.05).HE staining showed that compared with the control group,tumor cells in the intervention groups showed apoptosis,and the number of necrotic lesions was increased.The results of transmission electron microscope showed that the cell injury was more serious and the edema was severe in the low and high doses of Shenqi Fuzheng Injection combined with cisplatin intervention group than that in the cisplatin group.Immunohistochemistry method and western blot showed that the expression of c-Myc in tumor tissue was up-regulated in the cisplatin alone intervention group,while the expressions of ABCC1,ALDH1 and c-Myc in xenografts were significantly down-regulated in different doses of Shenqi Fuzheng Injection combined with cisplatin groups(P<0.05).Conclusion Shenqi Fuzheng Injection combined with cisplatin can down-regulate the expressions of ABCC1,ALDH1 and c-Myc,inhibit the tumor stemness-resistance axis regulated by c-Myc and improve the cisplatin sensitivity of lung adenocarcinoma drug-resistant cells.
作者
刘兵
刘文俊
赵秋宇
孙冶
王淳
LIU Bing;LIU Wenjun;ZHAO Qiuyu;SUN Ye;WANG Chun(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Shenyang Medical College,Shenyang 110034,Liaoning,China)
出处
《辽宁中医杂志》
北大核心
2025年第10期193-197,I0010,共6页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(82174254)
国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023034)
辽宁省教育厅青年项目(LJKQZ20222412)
辽宁省自然科学基金面上项目(2024-MSLH-288)。
关键词
参芪扶正注射液
肺腺癌
顺铂耐药
移植瘤
Shenqi Fuzheng Injection(参芪扶正注射液)
lung adenocarcinoma
cisplatin resistance
transplantable tumor
