1. PDIA4 在肾癌细胞舒尼替尼耐药中的作用研究.
- Author
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唐麒麟, 柯波亮, 何雏江, 徐子杰, 陈 磊, and 邵 怡
- Subjects
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RENAL cell carcinoma , *PROTEIN disulfide isomerase , *RENAL cancer , *CANCER cell proliferation , *SUNITINIB - Abstract
Objective: To establish a renal cell carcinoma sunitinib-resistant cell line and to explore the mechanism by which protein 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 lentiviral 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 sensitivity 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). Conclusion: PDIA4 is associated with sunitinib resistance in renal cell carcinoma by the mechanism of inhibition of apoptosis causing sunitinib resistance in renal cell carcinoma, and targeting PDIA4 reverses the resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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