Caspase12和Caspase3在内质网应激介导的HCC细胞凋亡中的作用  

Role of Caspase12 and Caspase3 in endoplasmic reticulum stress mediated apoptosis of HCC

作　　者：温静静[1] 董玉娟 王大壮 王世凯 陈红芳[1] WEN Jingjing;DONG Yujuan;WANG Dazhuang;WANG Shikai;CHEN Hongfang(Department of Pathology,Weifang Yidu Central Hospital,Weifang 262500,Shandong,China;Department of Hepatobiliary Surgery,Weifang Yidu Central Hospital,Weifang 262500,Shandong,China)

机构地区：[1]潍坊市益都中心医院病理科,山东潍坊262500 [2]潍坊市益都中心医院肝胆外科,山东潍坊262500

出　　处：《贵州医科大学学报》2022年第2期197-202,共6页Journal of Guizhou Medical University

基　　金：潍坊市卫健委科研项目(wfwsjk_2019_096)。

摘　　要：目的探讨Caspase12与Caspase3的表达变化在内质网应激(ERS)介导的肝细胞肝癌(HCC)发生细胞凋亡过程中的作用。方法选取25例临床病理分级为Ⅰ-Ⅱ级(高分化)的HCC组织作为HCCⅠ-Ⅱ级组、25例Ⅲ-Ⅳ级(低分化)HCC组织作为HCCⅢ-Ⅳ级组,分别各取25例癌旁组织作为癌旁对照组;采用原位未端标记法(TUNEL)法检测各组肝组织的细胞凋亡情况,免疫组织化学法、Western Blot检测各组肝组织中Caspase12、Caspase3及GRP78蛋白表达,Real-time PCR检测各组肝组织中Caspase 12、Caspase 3及GRP 78 mRNA表达水平。结果与相应癌旁对照组比较,TUNEL法检测结果表明,HCCⅠ-Ⅱ级、Ⅲ-Ⅳ级组细胞的凋亡数目升高(P<0.05);免疫组织化学法、Western Blot及Real-time PCR检测显示HCCⅠ-Ⅱ级及HCCⅢ-Ⅳ级组中Caspase3与GRP78蛋白及mRNA表达增加(P<0.05);Caspase12蛋白及mRNA表达在各组间比较,差异无统计学意义(P>0.05)。结论ERS参与了HCC发展过程中的细胞凋亡,且是通过介导Caspase12以外的信号通路激活Caspase3执行的细胞凋亡。Objective To investigate the role of expression changes of Caspase-3 and Caspase-12 in endoplasmic reticulum stress(ERS)mediated apoptosis of hepatocellular carcinoma cell(HCC).Methods Twenty-five clinical specimens of HCC with pathological grades of gradeⅠ-Ⅱ(highly differentiated)were selected as HCCⅠ-Ⅱgroup,and 25 specimens of HCC with gradeⅢ-Ⅳ(poorly differentiated)as HCCⅢ-Ⅳgroup.Their corresponding adjacent tissues were collected and taken as their controls,respectively.TUNEL assay was used to detect the apoptosis of liver tissue cells in each group.The protein expression levels of Caspase12,Caspase3,and GRP78 in hepatocellular carcinoma and adjacent liver tissues were measured by immunohistochemistry(IHC)and Western blot,while their mRNA expression levels were measured by Real-time PCR.Results When compared with the corresponding adjacent tissues,TUNEL assay showed that the number of apoptotic cells in HCC gradeⅠ-ⅡandⅢ-Ⅳwere significantly increased(P<0.05).IHC,Western blot,and Real-time PCR showed that both protein and mRNA expression levels of caspase 3 and GRP78 were significantly increased in HCC gradeⅠ-Ⅱ(highly differentiated)and HCC gradeⅢ-Ⅳ(poorly differentiated,P<0.05).Furthermore,there was no significant difference in Caspase12 at both protein and mRNA levels among the groups(P>0.05).Conclusion ERS is involved in apoptosis during HCC development via activating Caspase3 other than Caspase12.

关 键 词：内质网应激 肝细胞肝癌 半胱氨酸蛋白酶12 半胱氨酸蛋白酶3 细胞凋亡 

分 类 号：R735.7[医药卫生—肿瘤]