摘要
目的探讨补中益气汤调节A549/DDP荷瘤裸鼠移植瘤GSK-3β活性表达干预顺铂耐药的机制研究。方法体外培养A549/DDP细胞,接种于BALB/c nu/nu裸鼠腋窝皮下,8 d后成瘤,隔天开始分别给予低剂量(1.46 g·kg^(-1))、中剂量(2.91 g·kg^(-1))、高剂量(5.82 g·kg^(-1))补中益气汤治疗25d。30只裸鼠随机分为A549/DDP荷瘤对照组(A组)、A549/DDP荷瘤+顺铂组(B组)、A549/DDP荷瘤+顺铂+低剂量补中益气汤组(C组)、A549/DDP荷瘤+顺铂+中剂量补中益气汤组(D组)、A549/DDP荷瘤+顺铂+高剂量补中益气汤组(E组),测量移植瘤质量并计算药物抑瘤率;蛋白质印迹法检测移植瘤组织中胞浆、胞核的GSK-3β、p-GSK-3β^(ser9)、p-GSK-3β^(tyr216)蛋白表达。结果顺铂联合补中益气汤可使移植瘤质量逐渐缩小,抑瘤率逐渐增加,呈现剂量依赖性。顺铂联合补中益气汤可显著下调移植瘤细胞胞浆p-GSK-3β^(ser9)的表达,而对GSK-3β、p-GSK-3β^(tyr216)的表达均无显著影响。结论补中益气汤下调p-GSK-3β^(ser9)表达,增加胞浆中GSK-3β的活性表达进而改善肺腺癌的顺铂耐药性。
Objective To explore mechanism of Buzhongyiqi Decoction intervening in cisplatin resistance through regulating expression and activity of GSK-3β.Methods A549/DDP cells were cultured in vitro and injected into the armpit of BALB/c nude mice.The tumor was observed on the 8th day.Next day,low dose(1.46g·kg^(-1)),medium dose(2.91g·kg^(-1))and high dose(5.82g·kg^(-1))of Buzhong yiqi decoction were given until 25 days later.In this experiment,thirty nude mice had been divided into five groups randomly.Nothing was injected into the mice in group A.Cisplatin was injected into the mice in group B.Cisplatin and low-dose Buzhongyiqi Decoction were injected into the mice in group C.Cisplatin and medium-dose Buzhong yiqi decoction were injected into the mice in group D.Cisplatin and high-dose Buzhongyiqi Decoction were injected into the mice in group E.The quality of transplanted tumor was measured and the tumor inhibition rate was calculated after the experiment.The protein expressions of GSK-3β,p-GSK-3β^(ser9)and p-GSK-3β^(tyr216)in cytoplasm and nucleus of transplanted tumor cells were detected through Western blot.Results The quality of transplanted tumor turned to decrease and the tumor inhibition rate turned to increase with the increase of TCM dosage.The cytoplasmic expression of p-GSK-3β^(ser9)was down-regulated with administration of the cisplatin combined with Buzhongyiqi Decoction significantly,while those of GSK-3βand p-GSK-3β^(tyr216)had no significance.Conclusion Buzhongyiqi Decoction improved cisplatin resistance through down-regulating the cytoplasmic expression of p-GSK-3β^(ser9).
作者
宋飞飞
刘彬
牟琪瑞
付权泽
王淳
刘春英
高原
SONG Fei-fei;LIU Bin;MU Qi-rui;FU Quan-ze;WANG Chun;LIU Chun-ying;GAO Yuan(Department of Internal Medicine of Traditional Chinses Medicine,Hainan Medical College,Haikou 571100;Department of Basic Chinses Medicine,Hainan Medical College,Haikou 571100;Faculty of Graduate Studies,Liaoning University of Chinese Traditional Medicine,Shenyang 110032,China;Nursing College,Liaoning University of Chinese Traditional Medicine,Liaoning University of Chinese Traditional Medicine,Shenyang 110032,China;Department of Hygiene and Biology,Liaoning University of Chinese Traditional Medicine,Shenyang 110032,China;Department of Pathology,Liaoning University of Chinese Traditional Medicine,Shenyang 110032,China)
出处
《解剖科学进展》
CAS
2022年第6期665-668,共4页
Progress of Anatomical Sciences
基金
国家自然科学基金(81973735,81773784)
