Effect and mechanism of SOX2 expression changes on paclitaxel sensitivity in non-small-cell lung cancer A549 cells
HU Shasha
LI Kexiu
ZHANG Wei
Abstract：Objective To observe the effect of changes in the expression of sex-determining region Y-box2(SOX2)on the sensitivity of human non-small-cell lung cancer cell line A549 to paclitaxel(PTX),and to explore the relevant mechanism based on the regulation of voltage-gated chloride channel-3(ClC-3).Methods We cultivated A549 cells and induced PTX-resistant A549 cell line(A549/R)by gradually increasing the dosages of PTX intermittently.MTT assay was used to detect the sensitivity of A549 and A549/R cells to PTX and we calculated the half maximal inhibitory concen-tration(IC50).Western blotting was used to detect resistance-related proteins(ABCC2,ABCC10C,and MDR1),SOX2 protein,and ClC-3 protein.The qRT-PCR was used to detect SOX2 ClC-3 mRNA.We transfected A549 cells with SOX2 knockdown plasmid,SOX2 overexpression plasmid,and SOX2 overexpression plasmid+ClC-3 knockdown plasmid,respectively,detected ClC-3 mRNA and protein in transfected and untransfected cells,and calculated the IC50 of PTX.Results The IC50 of PTX on A549-R cells was higher than that on A549 cells(P<0.01);the expression levels of ABCC2,ABCC10C,MDR1,SOX2,ClC-3 proteins and SOX2,ClC-3 mRNA in A549-R cells were higher than those in A549 cells(all P<0.01).The expression levels of ClC-3 mRNA and protein,and the IC50 of PTX in A549 cells with low SOX2 expression were lower than those in A549 cells(all P<0.05);the expression levels of ClC-3 mRNA and protein,and the IC50 of PTX in A549 cells with SOX2 overexpression were higher than those in A549 cells(all P<0.05);there was no significant difference in the IC50 of PTX between A549 cells with overexpression of SOX2 and low expression of ClC-3 and A549 cells(P>0.05).Conclusion SOX2 expression increased in A549 cells resistant to PTX,and the regulatory effect of SOX2 on PTX sensitivity in A549 cells may be related to the regulation of ClC-3 expression.
Keywords：non-small-cell lung cancerpaclitaxeldrug resistancesex-determining region Y-box2chloride ion voltage-gated channel-3
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 46-50 )