益气除痰方对肺癌移植瘤小鼠内质网应激蛋白GRP78/BIP、caspase-12的影响  

Effects of Qi-Benefiting Phlegm-Eliminating Formula on GRP78 /BIP and Caspase-12 in Lung Cancer Xenografts Model Mice

作　　者：李元滨[1] 杨建猛[1] 方若鸣[1] 陈文卿[1] 林丽珠[2] 

机构地区：[1]广州中医药大学第一临床医学院,广东省广州市机场路12号510405 [2]广州中医药大学第一附属医院

出　　处：《中医杂志》2014年第11期955-958,共4页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81273963);广东省教育厅高层次人才培养项目(2010-79)

摘　　要：目的探讨益气除痰方治疗肺癌的可能作用机制。方法 15只BALB/c小鼠采用人肺腺癌细胞A549建立人肺癌小鼠皮下移植瘤模型,随机分为模型组和益气除痰方低、高剂量组,每组5只。益气除痰方低、高剂量组分别予益气除痰方生药量27.3g/(kg·d)、54.6g/(kg·d),造模后第8天开始灌胃,每天1次,连续2周;模型组予同体积生理盐水。采用常规HE染色法、透射电镜观察各组小鼠移植瘤组织形态学改变;应用免疫组织化学法、免疫蛋白印迹法检测GRP78/BIP、caspase-12蛋白的表达。HE染色观察各组小鼠主要脏器病理学改变。结果益气除痰方治疗后移植瘤细胞呈现凋亡形态学改变,以高剂量较典型。与模型组比较,益气除痰方低、高剂量组GRP78/BIP表达下降,caspase-12、cleaved caspase-12表达升高(P<0.05或P<0.01),且益气除痰方高剂量组优于益气除痰方低剂量组(P<0.01)。各组小鼠主要脏器无明显病理学改变。结论益气除痰方诱导肺癌细胞发生凋亡具有剂量依赖性,其机制可能与内质网应激凋亡特异性蛋白caspase-12活化,启动内质网应激凋亡通路有关。Objective （QBPEF） for lung cancer. To research the possible Methods Fifteen BALB/c els with human lung adenocarcinoma cell A549, and the mechanism of Qi-Benefiting Phlegm-Eliminating Formula mice were selected to establish lung cancer xenografts rood- mice were randomized into model group, QBPEF low-dose group and QBPEF high-dose groups, with 5 in each. The QBPEF low-dose and high-dose groups were given 27.3 g/ （kg d） or 54. 6g/ （kg d） crude drug of QBPEF each day respectively from the 8th day after modeling for 2 consecutive weeks. The model group was given the same volume of normal saline. The morphological changes in transplanted tumor tissue were observed with HE staining and transmission electron microscopy. The expressions of GRP78/BIP and caspase-12 were detected with immunohistochemistry and Western blotting. The pathological changes in major organs were observed with HE staining. Results The transplanted tumor cells showed a morphological change of apoptosis in QBPEF groups after treatment, especially in the QBPEF high-dose group. Comparing with the model group, the expression of GRP78/BIP was significantly decreased but the expressions of caspase-12 and cleaved easpase-12 were significantly increased in QBPEF groups （ P 〈 0.05 or P 〈 0.01 ）, especially in the QBPEF high- dose group （P 〈0.01 ）. There was no obvious morphological change in major organs. Conclusion QBPEF can in- duce apoptosis in lung cancer cells with a dose-dependent manner, which may be related to activating caspase-12 and starting the endoplasmic reticulum stress apoptosis pathway.

关 键 词：肺癌 益气除痰方 内质网应激 细胞凋亡 

分 类 号：R734.2[医药卫生—肿瘤]