佛波酯增强顺铂的抗肿瘤活性及降低其肾毒性的作用研究  

Study of TPA on enhancing the anti-tumor effects of cisplatin and reducing its renal toxicity

作　　者：王新丽 许霞青 方寒冰 郭玉忠[2] WANG Xinli;XU Xiaqing;FANG Hanbing;GUO Yuzhong(Department of Pharmacy,Zhengzhou Central Hospital of Zhengzhou University,Zhengzhou 450001,Henan,China;Basic Medical College of Zhengzhou University,Zhengzhou 450001,Henan,China)

机构地区：[1]郑州大学附属郑州中心医院药学部,河南郑州450001 [2]郑州大学基础医学院,河南郑州450001

出　　处：《中国临床药理学与治疗学》2022年第5期535-543,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：吴阶平医学基金会(320.6750.2021-02-57);河南省高等学校重点科研项目(22A310029)。

摘　　要：目的:探讨佛波酯(TPA)对顺铂(CP)的抗肿瘤作用及肾毒性的影响。方法:MTT法检测TPA在肺癌细胞A549、SPC-A-1中对CP抑制肿瘤细胞增殖作用的影响;一次性尾静脉注射大剂量CP考察TPA对CP急性毒性的影响;采用荷瘤小鼠模型考察TPA对CP抑瘤率和肾毒性的影响;并检测TPA对CP引起肾脏氧化应激的作用。结果:1 ng/mL TPA显著增强CP对肺癌细胞增殖的抑制作用;急性毒性实验中TPA降低CP的毒性,显著延长动物的存活时间;荷瘤小鼠模型中TPA联合CP组瘤重(P<0.05)、血肌酐(P<0.05)和尿素氮水平(P<0.01)均明显低于CP组;HE染色结果显示TPA联合CP组中小鼠肾组织损伤明显减轻;与CP组相比,肾组织中丙二醛含量在TPA联合CP组中下降显著(P<0.01),而谷胱甘肽含量和超氧化物歧化酶活性在联合组中明显上升(P<0.05)。结论:TPA增强CP对肺癌细胞的增殖抑制作用,且抑制荷瘤小鼠肿瘤生长;TPA同时可降低CP的肾毒性,该作用可能与TPA抑制了CP引起的肾脏氧化应激有关。AIM:To investigate the effects of phorbol ester(TPA)on the anti-tumor effect and renal toxicity of cisplatin(CP).METHODS:MTT assay was used to examine the effect of TPA on the proliferation inhibition of CP in A549 and SPC-A-1 lung cancer cells.Also the effect of TPA on acute toxicity of CP was observed by once injection of high dose CP through caudal vein;The tumor-bearing mice model was explored to investigate the effect of TPA on tumor inhibition ratio and renal toxicity of CP in vivo.And the effect of TPA on renal oxidative stress induced by CP was detected.RESULTS:1 ng/mL TPA could significantly enhance the inhibitory effect of CP on cell proliferation.In acute toxicity test,TPA could significantly reduce the toxicity of CP and prolong the survival time of animals.And the tumor weight(P<0.05),serum creatinine(P<0.05)and urea nitrogen levels(P<0.01)in TPA combined with CP group were significantly lower than those in CP group.Meanwhile,the results of HE staining showed that the renal tissue damage was significantly reduced in the combined group compared with CP group.The contents of MDA in renal tissue were decreased(P<0.01).However,the contents of GSH and the activity of SOD were increased(P<0.05)in TPA and CP combined group.CONCLUSION:TPA can enhance the inhibitory effect of CP on cell proliferation and inhibit tumor growth in tumor-bearing mice.At the same time,TPA can reduce the renal toxicity of CP,which may be related to the inhibition of renal oxidative stress induced by CP.

关 键 词：佛波酯 顺铂 细胞增殖 肾毒性 氧化应激 

分 类 号：R965.2[医药卫生—药理学]