一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cellular Oncology >>article
Cellular Oncology

Cellular Oncology

IF: 4.8
Download PDF

Nilotinib in combination with sunitinib renders MCL-1 for degradation and activates autophagy that overcomes sunitinib resistance in renal cell carcinoma.

Published:1 August 2024 DOI: 10.1007/s13402-024-00927-9 PMID: 38393513
Tingyu Liu,?Xin Yue,?Xue Chen,?Ru Yan,?Chong Wu,?Yunzhi Li,?Xianzhang Bu,?Hui Han,?Ran-Yi Liu

Abstract

Purpose: Sunitinib is a recommended drug for metastatic renal cell carcinoma (RCC). However, the therapeutic potential of sunitinib is impaired by toxicity and resistance. Therefore, we seek to explore a combinatorial strategy to improve sunitinib efficacy of low-toxicity dose for better clinical application.

Methods: We screen synergistic reagents of sunitinib from a compound library containing 1374 FDA-approved drugs by in vitro cell viability evaluation. The synergistically antiproliferative and proapoptotic effects were demonstrated on in vitro and in vivo models. The molecular mechanism was investigated by phosphoproteomics, co-immunoprecipitation, immunofluorescence and western-blot assays, etc. RESULTS: From the four-step screening, nilotinib stood out as a potential synergistic killer combined with sunitinib. Subsequent functional evaluation demonstrated that nilotinib and sunitinib synergistically inhibit RCC cell proliferation and promote apoptosis in vitro and in vivo. Mechanistically, nilotinib activates E3-ligase HUWE1 and in combination with sunitinib renders MCL-1 for degradation via proteasome pathway, resulting in the release of Beclin-1 from MCL-1/Beclin-1 complex. Subsequently, Beclin-1 induces complete autophagy flux to promote antitumor effect.

Conclusion: Our findings revealed that a novel mechanism that nilotinib in combination with sunitinib overcomes sunitinib resistance in RCC. Therefore, this novel rational combination regimen provides a promising therapeutic avenue for metastatic RCC and rationale for evaluating this combination clinically.

Substances (17)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Nilotinib 641571-10-0 C28H22F3N7O 513 suppliers $10.00-$1430.00
Nilotinib 641571-10-0 C28H22F3N7O 513 suppliers $10.00-$1430.00
Nilotinib 641571-10-0 C28H22F3N7O 513 suppliers $10.00-$1430.00
Nilotinib 641571-10-0 C28H22F3N7O 513 suppliers $10.00-$1430.00
Sunitinib 557795-19-4 C22H27FN4O2 460 suppliers Inquiry
Sunitinib 557795-19-4 C22H27FN4O2 460 suppliers Inquiry
Sunitinib 557795-19-4 C22H27FN4O2 460 suppliers Inquiry
Sunitinib 557795-19-4 C22H27FN4O2 460 suppliers Inquiry
CHLOROQUINE 54-05-7 C18H26ClN3 218 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 218 suppliers $5.00-$1550.00

Similar articles

古蔺县| 柯坪县| 吐鲁番市| 拉孜县| 华阴市| 新丰县| 东平县| 通化县| 沂南县| 潞城市| 新建县| 会宁县| 盐边县| 临漳县| 开封市| 自贡市| 富蕴县| 平顺县| 永济市| 保山市| 大关县| 扎赉特旗| 射阳县| 梁山县| 开平市| 元谋县| 前郭尔| 黄骅市| 禄丰县| 九江市| 延吉市| 稷山县| 景宁| 连州市| 上高县| 宁都县| 长海县| 石嘴山市| 商丘市| 河西区| 申扎县|