Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP.
Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP.
复制标题
DOI：
10.3892/or.2014.3184
复制
发表时间：
2014-07
期刊：
影响因子：
4.2
通讯作者：
Li Sun;Lili Liu;Xiangqiang Liu;Yafang Wang;Mengbin Li;L. Yao;Jianjun Yang;G. Ji;Changcun Guo;Yanglin Pan;Shuhui Liang;Biao-luo Wang;Jie Ding;Hongwei Zhang;Yongquan Shi
中科院分区：
文献类型：
--
作者：
Li Sun;Lili Liu;Xiangqiang Liu;Yafang Wang;Mengbin Li;L. Yao;Jianjun Yang;G. Ji;Changcun Guo;Yanglin Pan;Shuhui Liang;Biao-luo Wang;Jie Ding;Hongwei Zhang;Yongquan Shi
癌细胞与细胞外基质（ECM）的粘附导致一种新的获得性化疗药物耐药表型，称为细胞粘附介导的耐药（CAM-DR）。我们前期的研究提示粘附分子MGr 1-Ag/37 LRP可能促进胃癌细胞的多药耐药。因此，我们研究了MGr 1-Ag/37 LRP结合诱导的粘附，及其在CAM-DR中的作用。初步研究表明，在粘附到ECM后，多药耐药胃癌细胞系SGC 7901/VCR和SGC 7901/ADR显示出显著高于非耐药SGC 7901细胞的平均粘附细胞数。然后，我们研究了粘附层粘连蛋白的胃癌细胞中MGr 1-Ag/37 LRP的表达。Western blotting、RT-PCR和双荧光素酶报告基因检测结果表明，层粘连蛋白可诱导MGr 1-Ag/37 LRP的表达和活性。体外和体内实验表明，针对MGr 1-Ag/37 LRP的小干扰RNA可显著降低SGC 7901/VCR细胞中的CAM-DR。体内和体外分析显示，MGr 1-Ag/37 LRP结合可通过增加P-糖蛋白和多药相关蛋白的表达，减少细胞内药物蓄积，并通过调节Bcl-2和Bax的表达，抑制药物诱导的细胞凋亡。这些结果表明，MGr 1-Ag/37 LRP有助于胃癌细胞中层粘连蛋白介导的CAM-DR，并且是逆转胃癌中这种现象的潜在有效靶点。
Adhesion of cancer cells to the extracellular matrix (ECM) causes a novel acquired chemotherapeutic drug‑resistant phenotype, referred to as cell adhesion-mediated drug resistance (CAM-DR). Our previous studies suggested that the adhesion molecule MGr1-Ag/37LRP may promote multidrug resistance in gastric cancer cells. Therefore, we investigated MGr1-Ag/37LRP binding-induced adhesion, and its role in CAM-DR. Initial studies revealed that, after adhesion to the ECM, the multidrug-resistant gastric cancer cell lines SGC7901/VCR and SGC7901/ADR showed significantly higher mean adhesive cell numbers than non‑resistant SGC7901 cells. We then investigated expression of MGr1-Ag/37LRP in gastric cancer cells adhering to laminin. Western blotting, RT-PCR and dual-luciferase reporter assays showed that laminin induced MGr1-Ag/37LRP expression and activity. In vitro and in vivo assays revealed that small interfering RNA against MGr1-Ag/37LRP significantly reduced CAM-DR in SGC7901/VCR cells. In vivo and in vitro analyses revealed that binding of MGr1-Ag/37LRP decreased intracellular drug accumulation by increasing P-glycoprotein and multidrug-associated protein expression, and inhibited drug-induced apoptosis by regulating Bcl-2 and Bax expression. These results indicate that MGr1-Ag/37LRP contributes to laminin-mediated CAM-DR in gastric cancer cells, and is a potentially effective target for reversing this phenomenon in gastric cancer.