MUC13/HER2分子轴对胆管癌细胞恶性生物学行为和化疗耐药性的影响  

Influences of MUC13/HER2 molecular axis on malignant biological behavior and chemotherapy resistance of cholangiocarcinoma cells

作　　者：周通[1] 张晓霞 张国华[1] 牛海峰 ZHOU Tong;ZHANG Xiaoxia;ZHANG Guohua;NIU Haifeng(Department of General Surgery,Affiliated Hospital of Qinghai University,Qinghai Xining 810001,China;Department of Gastroenterology,Affiliated Hospital of Qinghai University,Qinghai Xining 810001,China)

机构地区：[1]青海大学附属医院普通外科学一科,青海西宁810001 [2]青海大学附属医院消化内科,青海西宁810001

出　　处：《现代肿瘤医学》2024年第13期2334-2340,共7页Journal of Modern Oncology

基　　金：青海大学附属医院中青年科研基金项目(编号:ASRF-2021-YB-20)。

摘　　要：目的:探讨黏蛋白13(MUC13)/人类表皮生长因子受体2(HER2)分子轴对胆管癌细胞(CCA)恶性生物学行为和化疗耐药性的影响。方法:选取2020年08月至2022年08月于本院就诊并接受手术治疗的60例CCA患者,免疫组化检测MUC13、HER2阳性表达;qRT-PCR检测CCA细胞系(QBC939、TFK-1、HuCCT-1)及胆管上皮细胞系HIBEpiC中MUC13、HER2 mRNA表达;然后以QBC939细胞为研究对象,设置对照组、sh-MUC13(MUC13的shRNA特异性抑制)组、sh-NC(阴性对照)组、sh-MUC13+pcDNA 3.1(空载体)组、sh-MUC13+pcDNA 3.1-HER2(HER2过表达载体)组;流式细胞仪检测上述各组QBC939细胞凋亡率变化;CCK-8检测各组QBC939细胞活力及耐药性;qRT-PCR检测各组QBC939细胞MUC13、HER2 mRNA表达;Transwell检测各组QBC939细胞侵袭及迁移;Western blot检测各组QBC939细胞MUC13、HER2、Bcl-2相关X蛋白(Bax)、细胞增殖相关核抗原(Ki-67)蛋白表达。结果:MUC13、HER2在癌组织中的阳性表达均显著增加(P<0.05);QBC939细胞中MUC13、HER2 mRNA表达增加最为显著(P<0.05);与对照组、sh-NC组相比,sh-MUC13组细胞增殖活力及耐药性、侵袭与迁移数、MUC13、HER2、Ki-67表达显著下降,凋亡率及Bax表达显著增加(P<0.05);与sh-MUC13+pcDNA 3.1组相比,sh-MUC13+pcDNA 3.1-HER2组细胞增殖活力、耐药性、侵袭与迁移数、MUC13、HER2、Ki-67表达显著增加,凋亡率及Bax表达显著下降(P<0.05)。结论:沉默MUC13表达有助于抑制QBC939细胞恶性生物学行为,降低其耐药性,可能与抑制HER2表达有关。Objective:To investigate the influences of mucin 13(MUC13)/human epidermal growth factor receptor 2( HER2) molecular axis on the malignant biological behavior and chemotherapy resistance of cholangiocarcinoma cells( CCA).Methods:Sixty patients with CCA who received surgical treatment in our hospital from August 2020 to August 2022 were selected.Immunohistochemical tests were conducted to detect the positive expression of MUC13 and HER2.QRT-PCR was used to detect the mRNA expressions of MUC13 and HER2 in CCA cell lines( QBC939,TFK-1,Hu CCT-1) and bile duct epithelial cell line HIBEpi C.Then,taking QBC939 cells as the research object,the control group,sh-MUC13( shRNA-specific inhibition of MUC13) group,sh-NC( negative control) group,sh-MUC13 + pc DNA 3.1( empty vector) group,and sh-MUC13 + pc DNA 3.1-HER2( HER2 overexpression vector)group were set.Flow cytometry was used to detect the changes of apoptosis rate of QBC939 cells in the above groups.CCK-8 was applied to detect the viability and drug resistance of QBC939 cells in each group.qRT-PCR was applied to detect the mRNA expression of MUC13 and HER2 in QBC939 cells in each group.Transwell was used to detect the invasion and migration of QBC939 cells in each group.Western blot was used to detect the protein expressions of MUC13,HER2,Bcl-2-associated X protein( Bax) and cell proliferation-related nuclear antigen( Ki-67) in QBC939 cells in each group.Results:The positive expression of MUC13 and HER2 in cancer tissues increased significantly( P < 0.05).The expression of MUC13 and HER2 mRNA increased most obviously in QBC9 3 9 cells( P <0.05).Compared with the control group and the sh-NC group,the cell proliferation activity,drug resistance,invasion and migration numbers,MUC13,HER2,and Ki-67 expressions in the sh-MUC13 group decreased obviously,the apoptosis rate and Bax expression increased obviously( P < 0.05).Compared with the sh-MUC13 + pc DNA 3.1group,the cell proliferation activity,drug resistance,invasion and migration numbers,MUC13,HER2,and Ki-67 expressions

关 键 词：MUC13/HER2 胆管癌细胞 化疗耐药性 恶性生物学行为 

分 类 号：R735.8[医药卫生—肿瘤]