摘要
Abstract
Objective To analyze the effects of silencing cluster of differentiation(CD)147 on the biological characteristics and epithelial-mesenchymal transition(EMT)in non-small cell lung carcinoma(NSCLC),and to explore the potential molecular mechanisms.Methods Tumor and adjacent normal tissue samples were retrospectively collected from 30 patients with NSCLC admitted to Tangdu Hospital of Air Force Military Medical University from August 2023 to March 2024.Human normal lung ep-ithelial cells BEAS-2B and NSCLC cell lines A549,NCI-H460 and NCI-H1299 were purchased from the Cell Bank of the Chi-nese Academy of Sciences.The levels of CD147 mRNA in NSCLC tissues and adjacent normal tissues,as well as in each cell line were detected by real-time fluorescence quantitative PCR(RT-qPCR).NCI-H460 cells were divided into control group,si-NC group,si-CD147 group,SC-79 group and si-CD147+SC-79 group;the effects of CD147 knockdown on proliferation,migration and apoptosis of NSCLC cells were detected by CCK-8,Transwell and flow cytometry.Western blot was performed to detect the expression of EMT-related markers including Neural-cadherin(N-cadherin),Vimentin,Epithelial-cadherin(E-cadher-in),Slug and Twist and proteins associated with the phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway.Results The expression level of CD147 mRNA in NSCLC tissues was significantly higher than that in adjacent normal tissues(1.64±0.25 vs 0.43±0.06),the difference was statistically significant(t=8.152,P<0.05).The ex-pression level of CD147 mRNA in NSCLC cells was significantly higher than that in human normal lung epithelial cells(1.24±0.13,3.31±0.37,2.16±0.29 vs 0.35±0.04,F=80.516,P<0.05).Compared with the control group,the si-CD147 group exhibited reduced cell proliferation rate(53.74%±4.07%vs 78.92%±6.23%),migration rate(19.57%±2.69%vs 37.24%±3.12%),and increased apoptosis rate(39.04%±2.74%vs 16.14%±2.14%)(t=5.548,7.068,12.036).N-cadherin(0.41±0.02 vs 1.01±0.02),Vimentin(0.36±0.04 vs 1.02±0.04),Slug(0.49±0.03 vs 1.02±0.03)and Twist(0.53±0.05 vs 1.03±0.04)protein expressions were decreased and E-cadherin(1.85±0.14 vs 0.98±0.02)protein expression was increased in NCI-H460 cells of si-CD147 group(t=12.766～36.742),the protein expression levels of P-PI3K(0.42±0.03 vs 1.01±0.03),p-AKT(0.45±0.03 vs 1.01±0.02)and p-mTOR(0.38±0.02 vs 0.99±0.02)in NCI-H460 cells of si-CD147 group were signifi-cantly decreased(t=8.377,7.286,9.694),the differences were statistically significant(all P<0.05).Compared with the SC-79 group,the si-CD147+SC-79 group exhibited significantly increased cell proliferation rate and migration rate,reduced apoptosis rate,enhanced EMT process and phosphor-PI3K/AKT/mTOR protein level(t=2.595～14.476),the differences were statistically significant(all P<0.05).SC-79 treatment reversed the effects of CD147 knockdown on cell biological behavior,EMT process and PI3K/AKT/mTOR pathway(t=2.595～14.476),the differences were statistically significant all P<0.05).Conclusions The high ex-pression of CD147 can induce EMT process through PI3K/AKT/mTOR pathway,promoting the proliferation and migration of tumor cells,while inhibiting cell apoptosis,thereby contributing to the development and progression of NSCLC.关键词
非小细胞肺癌/分化簇147/增殖/迁移/凋亡/上皮-间质转化/磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路Key words
non-small cell lung cancer/cluster of differentiation 147/proliferation/migration/apoptosis/epithelial-mesenchymal transition/PI3K/AKT/mTOR pathway分类
医药卫生
