Integrin β1对胃癌细胞SGC7901多药耐药性的影响  

Effect of integrin β1 on multidrug resistance in gastric cancer SGC-7901 cells

作　　者：邵棋[1] 曹斐[2] 李梅[1] 张艳[1] 

机构地区：[1]南通大学附属医院肿瘤化疗科,江苏南通226001 [2]苏州市立医院北区肿瘤内科,江苏苏州215008

出　　处：《中国病理生理杂志》2016年第12期2233-2238,共6页Chinese Journal of Pathophysiology

摘　　要：目的:探究整合素β1(integrinβ1)对胃癌多药耐药性的影响及可能的作用机制。方法:Western blot法及q PCR实验检测胃癌细胞株SGC-7901及胃癌耐药细胞株SGC-7901/DDP中integrinβ1的表达情况。采用integrinβ1反义寡核苷酸转染,敲减胃癌耐药细胞株SGC-7901/DDP中integrinβ1的表达,CCK-8法检测细胞活力,流式细胞术检测细胞凋亡,Western blot法检测integrinβ1、Bcl-2/Bax、cleaved caspase-3/caspase-3、细胞色素C(CytC)和p-AKT/AKT的蛋白水平。结果:耐药细胞株SGC7901/DDP中integrinβ1的mRNA及蛋白表达水平均明显高于亲本细胞株;并且在亲本细胞株SGC7901中加入顺铂、长春新碱及5-氟尿嘧啶等化疗药物刺激后,integrinβ1的蛋白表达水平明显升高。敲减integrinβ1的表达可诱导胃癌耐药细胞SGC7901/DDP的凋亡,增加细胞对化疗药物的敏感性;此外下调Bcl-2/Bax、p-AKT^(Ser473)和p-AKT^(Thr308)的蛋白水平,同时促进线粒体Cyt-C的释放,上调cleaved caspase-3的蛋白水平。结论:敲减胃癌顺铂耐药细胞SGC7901/DDP的integrinβ1表达可恢复细胞对化疗药物的敏感性,促进细胞经线粒体路径的凋亡,其机制可能与抑制AKT的磷酸化,阻断该信号通路有关。AIM：To study the effect of integrin β1 on multidrug resistance in gastric cancer and its possible mechanisms.METHODS：The expression of integrin β1 at mRNA and protein levels in the SGC-7901 cells and SGC-7901/DDP cells was determined by q PCR and Western blot.The expression of integrin β1 in the SGC-7901/DDP cells was silenced by antisense oligodeoxynucleotide.The cell viability was detected by the CCK-8 assay,the cell apoptosis were analyzed by flow cytometry,and the protein levels of integrin β1,Bcl-2/Bax,cleaved caspase-3/caspase-3,cytochrome C（ Cyt-C） and p-AKT/AKT were determined by Western blot.RESULTS：The expression of integrin β1 at both mRNA and protein levels was significantly upregulated in SGC-7901/DDP cells.The expression of integrin β1 was increased in SGC-7901 cells treated with chemotherapeutic agents such as cisplatin,paclitaxel and 5-fluorouracil.Knockdown of integrin β1induced apoptosis of SGC-7901/DDP cells with an increased sensitivity to the chemotherapeutic agents.Meanwhile,knockdown of integrin β1 downregulated the protein levels of Bcl-2/Bax,p-AKT^Ser473and p-AKT^Thr308,while promoted the release of Cyt-C and upregulated the protein level of cleaved caspase-3.CONCLUSION：Knockdown of integrin β1 increases the sensitivity of SGC-7901/DDP cells to the chemotherapeutic agents,and promotes the cell apoptosis via mitochondrial apoptosis pathway.The mechanism may be related to the attenuation of AKT pathway by inhibiting phosphorylations of AKT at Ser473 and Thr308.

关 键 词：整合素Β1 胃癌 多药耐药性 细胞凋亡 AKT 

分 类 号：R730.23[医药卫生—肿瘤] R735.2[医药卫生—临床医学]