Study on the Role of PDIA4 in Sunitinib Resistance of Renal Cancer Cells
Objective:To establish a renal cell carcinoma sunitinib-resistant cell line and to explore the mechanism by which pro-tein disulfide isomerase A4(PDIA4)regulates sunitinib resistance in renal cell carcinoma.Methods:A small-dose intermittent induction method was used to establish 786-O and OS-RC-2 resistant cell lines(786-OR and OS-RC-2R),qRT-PCR and Western blot were used to detect the expression of PDIA4 in drug-resistant renal carcinoma cell lines and non-drug-resistant renal carcinoma cell lines,and lentivi-ral infection was used to construct a stable overexpression or knockdown renal carcinoma cell line of PDIA4.The effect of PDIA4 on the proliferation of renal cancer cells was detected by CCK-8 assay;the expression of apoptosis-related proteins BCL2,BAX,Caspase3,Cleaved-Caspase3,and Caspase9 was detected by RT-qPCR and Western blot.Results:Compared with the control group of parental cells 786-O and OS-RC-2,the PDIA4 expression levels of drug-resistant cell lines 786-OR and OS-RC-2R are significantly increased(P＜0.05).Overexpression of PDIA4 promoted the growth and viability of renal cancer cells as well as decreased the sensitivity of renal cancer cells to sunitinib(P＜0.05),whereas knockdown of PDIA4 inhibited the growth and viability of renal cancer cells as well as elevated the sensi-tivity of renal cancer cells to sunitinib(P＜0.05).In addition,overexpression of PDIA4 inhibited the expression of pro-apoptotic proteins(P＜0.05),while knockdown of PDIA4 promoted the expression of pro-apoptotic proteins(P＜0.05).Conclusions:PDIA4 is associated with sunitinib resistance in renal cell carcinoma by the mechanism of inhibition of apoptosis causing sunitinib resistance in renal cell car-cinoma,and targeting PDIA4 reverses the resistance.
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