ITGA3 对非小细胞肺癌紫杉醇耐药性的 影响及机制.

Objective To study the effect of integrin subunit α3 (ITGA3) on paclitaxel resistance in non-small-cell lung cancer (NSCLC) and its mechanism. Methods Tumor tissues from 50 NSCLC patients treated with paclitaxel combined with cisplatin chemotherapy, A549/Tax (paclitaxel-resistant human lung adenocarcinoma) cells, human A549 cell line and human embryonic lung fibroblasts (MRC-5) were selected. RT-qPCR was used to detect the expression levels of ITGA3 mRNA in tissues and cells. A549/Tax cells were used as the research objects and were transfected with pcDNA3. 1- ITGA3 plasmid (oe-ITGA3) and pcDNA3. 1 empty vector (oe-NC), silencing ITGA3 small RNA (sh-ITGA3) and negative control (sh-NC), respectively, which were recorded as the oe-ITGA3 group, oe-NC group, sh-ITGA3 group and shNC group, respectively. Untreated A549/Tax cells were used as the control group. CCK-8 was used to detect the OD450 values at 24 and 48 h. Western blotting was used to detect the expression of EMT-related proteins [vimentin, E-cadherin, snail] and TGF-β, and immune escape protein [programmed death ligand-1 (PD-L1)]; RT-qPCR was used to detect the expression of ITGA3 mRNA in A549/Tax cells; Transwell assay was used to detect the migration and invasion abilities of A549/Tax cells. Results After treatment, the expression of ITGA3 mRNA in the tumor tissues was higher than that before treatment (P<0. 05). The expression levels of ITGA3 mRNA in the A549 cells and A549/Tax cells were higher than that in the MRC-5 cells (all P<0. 05). After treatment, Vimentin, snail, TGF-β and PD-L1 in the tumor tissues of NSCLC patients increased in comparison with those before treatment, while E-cadherin decreased (all P<0. 05) . Compared with the control group and the oe-NC group, the OD450 values at 24 and 48 h, the number of cell migration and invasion, the ITGA3 mRNA expression, the expression levels of Vimentin, snail, TGF-β and PD-L1 increased, and the expression of Ecadherin decreased in the oe-ITGA3 group (all P<0. 05). Compared with the control group and the sh-NC group, the OD450 values at 24 and 48 h, the number of cell migration and invasion, the ITGA3 mRNA expression, and the expression levels of Vimentin, snail, TGF-β and PD-L1 decreased, and the expression of E-cadherin increased in the sh-ITGA3 group (all P<0. 05). Conclusion Down-regulating ITGA3 expression can inhibit the drug resistance of NSCLC cells to paclitaxel, and its mechanism may be related to the inhibition of TGF-β expression. [ABSTRACT FROM AUTHOR]