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Cholesterol neutralized vemurafenib treatment by promoting melanoma stem?like cells via its metabolite 27?hydroxycholesterol

Cell Mol Life Sci. 2024-05; 
Xiaohong Wang, Feiliang Zhong, Tingting Chen, Hongbo Wang, Weifang Wang, Hongkai Jin, Chouyang Li, Xuan Guo, Ying Liu, Yu Zhang, Bo Li
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Proteins, Expression, Isolation and Analysis Protein lysates from cells were extracted in RIPA bufer, with 1×protease inhibitors cocktail. Equal number of proteins were resolved bySurePAGE? Plus, Bis–Tris (GenScript, M00725) Get A Quote

摘要

Vemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycho... More

關鍵詞

27-Hydroxycholesterol; Cholesterol metabolism; DHCR24; Melanoma.
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