The Construction Of Non-small Cell Lung Cancer Drug-resistant Strains And The Preliminary Study Of Their Drug-resistant Mechanisms

Lung cancer is one of the common malignancies on a global scale and it is a serious threat to the human body.Paclitaxel is a common first-line chemotherapeutic agent.It shows good therapeutic effects in the early stage of treatment,but drug resistance often occurs during the later treatment.The aim of this study was to identify key genes and signaling pathways associated with paclitaxel acquired resistance.Based on the second-generation sequencing technology,we performed whole-transcriptome sequencing of non-small cell lung cancer A549 cells and paclitaxel-resistant cells A549/Taxol.2870 differentially expressed genes were identified by transcriptome sequencing,among which 1503 genes were up-regulated and 1367 genes were down-regulated in A549/Taxol.Data mining based on the KEGG database,Pathways in cancer,P13K-Akt signaling pathway,and Rap1 signaling pathway are three signaling pathways that enrich the most differentially expressed genes.The Pathways in cancer pathway enriches 94 differentially expressed genes;P13K-Akt Signaling pathways enriched 78 differentially expressed genes;Rap1 signaling pathway signal pathway enriched 59 differentially expressed genes.In this study,10 differentially expressed genes were selected for verification by q-PCR method to ensure the accuracy of sequencing.The results showed that the sequencing data was accurate and reliable.Next,functional verification of DVL1 in the Wnt signaling pathway was performed.DVL1 was knocked out in A549/Taxol,and the IC50 value of A549/Taxol was significantly decreased,reducing the paclitaxel-induced apoptosis rate.The above results show that DVL1 gene plays a key role in regulating paclitaxel resistance in A549 cells and provides new clues for clinical chemotherapy treatment of non-small cell lung cancer.