益气除痰方对耐顺铂肺癌移植瘤生长及下调UPR诱导细胞凋亡的研究  

Effects of Yiqi Chutan Decoction on the growth of cisolatin-resistant cells of lung cancer and apoptosis of UPR-induced cells

作　　者：李元滨[1] 林丽珠[2] 杨建猛[1] 方若鸣[1] 李佳殷[1] 张景涛[1] 杨文娟[1] 

机构地区：[1]广州中医药大学,广州510405 [2]广州中医药大学第一附属医院,广州510405

出　　处：《中华中医药杂志》2014年第12期3906-3910,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金资助项目(No.81273963);广东省教育厅高层次人才培养项目(No.2010-79);广东省自然科学基金重点项目(No.S2012020010886)~~

摘　　要：目的:研究益气除痰方(以下简称中药)对耐顺铂肺癌移植瘤生长及内质网应激相关蛋白的影响。方法:建立耐顺铂肺癌裸鼠移植瘤模型,随机分为模型组、中药低、高剂量组;绘制各组移植瘤生长曲线,计算瘤重指数、抑瘤率;HE染色法、透射电镜观察各组瘤组织形态学,流式细胞术测定细胞凋亡率;免疫蛋白印迹法检测GRP78/Bip、PDI、PERK、p-PERK、e IF2α、p-e IF2α蛋白表达。结果:与模型组比较,中药高剂量组能明显抑制肿瘤生长,促进瘤细胞凋亡(P<0.05,P<0.01),并可明显下调GRP78/Bip、PDI、p-PERK、p-e IF2α蛋白表达(P<0.01);而PERK、e IF2α各组表达无统计学差异。结论:益气除痰方浓度依赖性抑制耐顺铂肺癌裸鼠移植瘤生长,其作用机制可能与其下调GRP78/Bip、PDI、p-PERK、p-e IF2α蛋白表达,弱化内质网未折叠蛋白反应,启动内质网凋亡通路有关。Objective： To observe the effects of Yiqi Chutan Decoction （YQCT） on the growth of subcutaneous xenografts with cisolatin-resistant lung cancer and endoplasmic reticulum stress related proteins. Methods： The model of lung cancer subcutaneous xenografts was established in nude mice using cisolatin-resistant lung cancer line A549/DDP. The mice were randomly divided into three groups： control group, low dosage group and high dosage group of YQCT. Xenografs growth curves was drawed and tumor weight ratio and inhibition rate were calculated. The histomorphology changes of tumor tissue were observed by HE staining and electron microscope. The apoptosis rate of cancer cells were detected by flow cytometry, and the expression levels of GRP78/Bip, PDI, PERK, p-PERK, eIF2α, p-eIF2α were measured by using western bloting. Results： Compared with the control group, the high dosage of YQCT could inhibit tumor growth and promote apoptosis of tumor cells significantly （P〈0.05, P〈0.01）. YQCT also could reduce the expression levels of GRP78/Bip, PDI, p-PERK, p-eIF2α （P〈0.01）, but the expression level of PERK and eIF2α of each group had no statistical significance. Conclusion： There is concentration dependent of YQCT in inhibiting of tumor cell growth in nude mouse by transplanting of cancer cells with cisplatin resistance, and the mechanism is related to the down-regulating the expressions of GRP78/Bip, PDI, p-PERK and p-eIF2α, weakening the expression of unfolded protein response （UPR）, and the initiating of endoplasmic reticulum apoptotic pathways.

关 键 词：肺癌 移植瘤 益气除痰方 凋亡 内质网未折叠蛋白反应 

分 类 号：R285.5[医药卫生—中药学]