细胞粘附分子-1抑制膀胱癌细胞侵袭转移的机制研究

Mechanism of cell adhesion molecule-1 inhibits the invasion and metastasis of bladder cancer cells

摘要:

目的：探讨细胞粘附分子-1(cell adhesion molecule-1，CADM1）过表达和干扰前后对人膀胱癌T24细胞恶性行为的影响及其机制。方法：利用前期构建的Ad-CADM1-T24、Ad-GFP1-T24、Ad-sh1-T24、Ad-GFP2-T24稳转细胞株，以T24细胞作为对照，Western blot检测细胞周期相关蛋白p27、cyclinD1、cyclinE1、CDK2，上皮-间充质转化（epithelial-mesenchymal transi－tion，EMT）相关蛋白E-cadherin、β-catenin、Vimentin，凋亡相关蛋白caspase-3、bcl-2、bax的表达情况；MTT法检测细胞增殖能力；Transwell侵袭实验检测细胞侵袭能力。结果：Western blot结果显示Ad-CADM1-T24细胞与其他细胞相比，凋亡相关蛋白caspase-3、bax表达量升高，bcl-2表达量降低；细胞周期相关蛋白p27表达量明显上调，cyclinD1、CDK2、cyclinE1表达量明显下调；EMT相关蛋白E-cadherin、β-catenin表达量明显上调，Vimentin表达量明显下调；MTT结果显示Ad-CADM1-T24细胞与其他细胞相比，细胞增殖明显受到抑制，差异具有统计学意义（P<0.05）；Transwell侵袭实验结果显示，Ad-CADM1-T24细胞与其他细胞相比，24 h细胞穿膜数量明显降低，差异具有统计学意义（P<0.05）。结论：CADM1过表达可明显抑制膀胱癌细胞的侵袭转移，其机制可能与抑制细胞增殖和EMT及促进细胞凋亡有关。

Abstract:

Objective：To investigate the effect of over or low expression of cell adhesion molecule-1（CADM1） on the malignant be－havior of human bladder cancer T24 cells. Methods：The stable expression cells of Ad-CADM1-T24，Ad-GFP1-T24，Ad-sh1-T24，Ad-GFP2-T24 were established before and were used in this study，and T24 cell was used as control. Western blot was used to detect the cell cycle-related protein p27，cyclinD1，cyclinE1，CDK2；and EMT-related protein E-cadherin，β-catenin，Vimentin；and apopto－sis-related protein caspase-3，bcl-2，bax. MTT was used to detect the cell reproductive capacity；and Transwell invasion was used to detect cell invasion ability. Results：Compared with other cells，in Ad-CADM1-T24 cell line，Western blot results showed that the ex－pressions of apoptosis-related protein caspase-3 and bax were increased，while those of bcl-2 were decreased；the expressions of cell cycle-related protein p27 were increased，while those of cyclinD1，CDK2 and cyclinE1 were decreased；the expressions of EMT-related protein E-cadherin and β-catenin were increased，while those of Vimentin were decreased. And the results of MTT showed that the cell proliferation was significantly inhibited in Ad-CADM1-T24 cell line，with statistically significant differences（P<0.05）. And the results of Transwell invasion showed that the number of cell membranes was significantly reduced in 24 h in Ad-CADM1-T24 cell line，with statistically significant differences（P<0.05）. Conclusion：Overexpression of CADM1 can significantly inhibit the invasion and metastasis of bladder cancer cells，the mechanism may be associated with inhibition of cell proliferation and EMT and promoting apoptosis.