Amiloride reduces fructosamine-3-kinase expression to restore sunitinib sensitivity in renal cell carcinoma

作者全名：Bai, Yuanyuan; You, Yiqing; Chen, Daoxun; Chen, Yongmei; Yin, Zhenjie; Liao, Shangfan; You, Bingyong; Lu, Dongming; Sun, Yingming; Wu, Lixian; Wu, Yongyang

作者地址：[Bai, Yuanyuan; Chen, Daoxun; Chen, Yongmei; Yin, Zhenjie; Liao, Shangfan; You, Bingyong; Lu, Dongming; Wu, Yongyang] Fujian Med Univ, Sanming Hosp 1, Dept Urol, Sanming 365100, Fujian, Peoples R China; [You, Yiqing] Chongqing Med Univ, Chinese Minist Educ, Key Lab Diag Med Designated, Chongqing 400016, Peoples R China; [Sun, Yingming] Fujian Med Univ, Sanming Hosp 1, Dept Oncol, Sanming 365100, Fujian, Peoples R China; [Wu, Lixian] Fujian Med Univ, Sch Pharm, Dept Pharmacol, Fuzhou, Peoples R China; [Wu, Lixian] Fujian Med Univ, Fujian Key Lab Nat Med Pharmacol, Fuzhou, Peoples R China

通信作者：Wu, YY (通讯作者)，Fujian Med Univ, Sanming Hosp 1, Dept Urol, Sanming 365100, Fujian, Peoples R China.; Sun, YM (通讯作者)，Fujian Med Univ, Sanming Hosp 1, Dept Oncol, Sanming 365100, Fujian, Peoples R China.; Wu, LX (通讯作者)，Fujian Med Univ, Sch Pharm, Dept Pharmacol, Fuzhou, Peoples R China.; Wu, LX (通讯作者)，Fujian Med Univ, Fujian Key Lab Nat Med Pharmacol, Fuzhou, Peoples R China.

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001247411700001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：27

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：The kidney is a vital organ responsible for water and sodium metabolism, while the primary function of amiloride is to promote the excretion of water and sodium. We investigated amiloride enhanced the sunitinib sensitivity in RCC. We found both sunitinib and amiloride displayed cytotoxicity and exerted the synergy effect in RCC cells in vivo and in vitro arrays. Protein expression profiles were screened via MS/TMT, revealing that FN3K was upregulated in the sunitinib group, and rescued in amiloride and the combination administration. Exogenous FN3K could promote proliferation, invasion and metastasis and decrease the sensitivity of Caki-1 cells to sunitinib, also, exogenous FN3K up -regulated VEGFR2 expression and activated AKT/mTOR signal pathway. More FN3K and VEGFR2 accumulated in R-Caki-1 cells and rescued by amiloride treatment. Co-IP and IF confirmed the interaction between FN3K and VEGFR2. In conclusion, FN3K depletion mediated VEGFR2 disruption promotes amiloride synergized the anti-RCC activity of sunitinib.

基金机构：Natural Science Foundation of Fujian Province, China [2019J01590]

基金资助正文：This study was supported by the Natural Science Foundation of Fujian Province, China (No. 2019J01590) supports the study.