槐耳颗粒逆转肝癌细胞对索拉非尼耐药的初步研究  

Preliminary Study on Reversal of Sorafenib Resistance of Hepatocellular Carcinoma Cells by Huaier Granule

作　　者：张正光[1] 刘冰 梁炜锋 沈存思 ZHANG Zheng-guang;LIU Bing;LIANG Wei-feng;SHEN Cun-si(School of MedicinE-&Holistic IntegrativE-Medicine,Nanjing University of ChinesE-Medicine,Nanjing,210023,China;Jiangsu Key Laboratory of Pediatric Respiratory Disease,ThE-Affiliated Hospital of Nanjing University of ChinesE-Medicine,Nanjing,210029,China)

机构地区：[1]南京中医药大学医学院·整合医学学院,江苏南京210023 [2]南京中医药大学附属医院,江苏省儿童呼吸疾病(中医药)重点实验室,江苏南京210029

出　　处：《南京中医药大学学报》2020年第1期83-87,共5页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金(81904029);江苏省自然科学基金(BK20151004);江苏省高等学校自然科学研究面上项目(19KJB360010);国家重点研发计划精准医学研究专项(2016YFC0905900)

摘　　要：目的初步探讨槐耳颗粒对索拉非尼(Sorafenib)耐药肝癌细胞BEL-7402/S的作用及其相关机制。方法 CCK-8法测定槐耳颗粒对BEL-7402/S细胞的增殖-毒性作用以及对Sorafenib的耐药逆转倍数;qPCR及Western blot法检测槐耳颗粒对BEL-7402/S细胞的缺氧诱导因子-1α(HIF-1α)及血管内皮生长因子(VEGF)mRNA和蛋白表达水平的影响。结果槐耳颗粒能够抑制BEL-7402/S细胞的活性;在无显著细胞毒性的剂量下,槐耳颗粒能够部分逆转BEL-7402/S细胞对Sorafenib的耐药,其耐药逆转倍数为2.08;qPCR结果显示槐耳颗粒可以下调BEL-7402/S细胞中HIF-1α的mRNA水平,但对VEGF的mRNA水平无显著性影响;Western blot结果显示槐耳颗粒可以降低HIF-1α、VEGF的蛋白表达水平。结论槐耳颗粒可能具有部分逆转BEL-7402/S细胞对Sorafenib耐药的作用,其机制可能与降低HIF-1α以及VEGF的表达水平有关。OBJECTIVE To investigate the effect and related mechanism of Huaier granule on Sorafenib-resistant hepatocellular carcinoma cells BEL-7402/S.METHODS The proliferation-toxicity effect of Huaier granule on BEL-7402/S cells and the reversal multiple of drug resistance to Sorafenib were measured by CCK-8 assays.The effects of Huaier granule on the mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)in BEL-7402/S cells were detected by qPCR and Western blot,respectively.RESULTS Huaier granule inhibited the activities of BEL-7402/S cells,and partially reversed the resistance of BEL-7402/S cells to Sorafenib at the dose of no significant cytotoxicity,and the reversal multiple of drug resistance was 2.08;the results of qPCR showed that Huaier granule may down-regulate the mRNA level of HIF-1α in BEL-7402/S cells,but had no significant effect on the mRNA level of VEGF.The results of Western blot showed that Huaier granule may down-regulate the protein levels of HIF-1α and VEGF in BEL-7402/S cells.CONCLUSION Huaier granule may partially reverse the drug resistance of BEL-7402/S cells to Sorafenib,and its mechanism may be related to the decrease of the expression of HIF-1α and VEGF.

关 键 词：槐耳颗粒 索拉非尼 肝癌 耐药 

分 类 号：R285.5[医药卫生—中药学]