Clear Cell Renal Cell Carcinoma (ccRCC), the most prevalent form of renal cell carcinoma (RCC), poses a significant threat to human health due to its rising morbidity and mortality rates. Sunitinib, a pivotal targeted drug for the treatment of ccRCC, presents a significant challenge due to the high susceptibility of ccRCC to resistance. HSP90 inhibitor AUY922 has demonstrated antitumor activity in a range of cancer types. However, its efficacy in combination with sunitinib for ccRCC treatment has not been evaluated. In this study, we employed bioinformatics, network pharmacology, and in vitro assays to verify that AUY922 inhibits cell viability, proliferation, and migration of ccRCC cell lines 786-O and ACHN, with IC50s of 91.86 mu M for 786-O and 115.5 mu M for ACHN. The effect of AUY922 enhancing the inhibitory effect of sunitinib on ccRCC was further confirmed. The CCK-8 assay demonstrated that the IC50 of sunitinib was reduced from 15.10 mu M to 11.91 mu M for 786-O and from 17.65 mu M to 13.66 mu M for ACHN, after the combined application of AUY922. The EdU assay and wound healing assay indicated that AUY922 augmented the inhibitory impact of sunitinib on the proliferation and migration of ccRCC cells. Western blot and RT-PCR analyses demonstrated that AUY922 increased the sensitivity of ccRCC cells to sunitinib by targeting the HIF-1a/VEGFA/VEGFR pathway. Our study represents the first investigation into the role and mechanism of AUY922 in enhancing the sensitivity of ccRCC to sunitinib. In
基金：
Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine [TRKYRC-xx202205]
第一作者机构：[1]Shanghai Jiao Tong Univ, Sch Med, Dept Urol, Tongren Hosp, Shanghai 200336, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Sch Med, Dept Urol, Tongren Hosp, Shanghai 200336, Peoples R China[2]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Hongqiao Int Inst Med, Shanghai 200336, Peoples R China[*1]1111 Xianxia Rd, Shanghai 200336, Peoples R China[*2]720 Xianxia Rd, Shanghai 200336, Peoples R China
推荐引用方式(GB/T 7714)：
Chen Zixuan,Jia Xing,Cai Yuesong,et al.AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments[J].HELIYON.2024,10(14):doi:10.1016/j.heliyon.2024.e34834.
APA：
Chen, Zixuan,Jia, Xing,Cai, Yuesong,Song, Ya,Tong, Yanjun...&Liu, Min.(2024).AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments.HELIYON,10,(14)
MLA：
Chen, Zixuan,et al."AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments".HELIYON 10..14(2024)
