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• W3160717281 startingPage "116214" @default.
• W3160717281 abstract "Hypoxia is one of the unique features of tumor physiology. Hypoxia inducible factor (HIF-1α), as a major transcription factor in response to hypoxia, has been considered as a promising tumor-specific target for anticancer therapy. The formation of a hypoxic microenvironment in tumors can decrease the curative effect of cytotoxic chemotherapeutic drugs. To promote the antitumor efficacy of chemotherapy by suppressing hypoxia, we designed and prepared a novel gemcitabine-based drug conjugate (GEM-5) containing a HIF-1α inhibitor (YC-1). As expected, GEM-5 showed excellent antiproliferative activity (IC50 = 0.03 μΜ under hypoxia) and remarkably induced the apoptosis of A2780 cells in vitro. Additionally, western blot analysis demonstrated that GEM-5 significantly down-regulated the expression of HIF-1α and up-regulated the expression of tumor suppressor p53. More importantly, GEM-5 effectively inhibited tumor growth in the A2780 xenograft mouse model and significantly ameliorated tumor hypoxia in vivo. This novel, simple, and effective strategy for overcoming tumor hypoxia and enhancing the antitumor effect of chemotherapeutic drugs has great potential in cancer therapy." @default.
• W3160717281 created "2021-05-24" @default.
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• W3160717281 date "2021-07-01" @default.
• W3160717281 modified "2023-09-23" @default.
• W3160717281 title "A gemcitabine-based conjugate with enhanced antitumor efficacy by suppressing HIF-1α expression under hypoxia" @default.
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• W3160717281 doi "https://doi.org/10.1016/j.bmc.2021.116214" @default.
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