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- W4224252034 endingPage "111842" @default.
- W4224252034 startingPage "111842" @default.
- W4224252034 abstract "Combination of immune- and chemo-therapy has become a new trend in cancer treatment. Food and Drug Administration (FDA)-approved immune-modulatory agent, thalidomide, can modulate the related proteins of upstream signaling pathway of programmed cell death-ligand 1 (PD-L1), including nuclear transcription factor κB (NF-κB), hypoxia inducible factor-1α (HIF-1α), epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3), all acting as key antitumor target proteins. In this work, we conjugated thalidomide with oxidized cisplatin to construct multi-functional Pt(IV) prodrugs, named thaliplatins 4–6, to investigate the anti-tumor effect of immuno- and chemo-therapy. Among them, thaliplatin 6 exerted remarkable cytotoxicity against the tested cancer cell lines, showing 15–26 and 9–20 times higher IC50 values than those of single cisplatin or the combination of cisplatin + thalidomide, respectively. Moreover, thaliplatin 6 could rapidly accumulated into cells, markedly triggered DNA damage, and induced cell S phase arrest and apoptosis, as well as inhibited cell migration and invasion in breast carcinoma cell line (MCF-7). Fluorescent confocal and western blotting experiments proved that 6 significantly regulated NF-κB, EGFR, HIF-1α and phosphor-signal transducer and activator of transcription 3 (p-STAT3), and simultaneously inhibited PD-L1 expression to interrupt programmed cell death 1 (PD-1)/PD-L1 signaling pathway, suggesting a synergistic action of cisplatin and thalidomide. Most strikingly, in vivo tests indicated that 6 effectively decreased tumor growth with no observable systemic toxicity, being superior to the anticancer efficacy of cisplatin." @default.
- W4224252034 created "2022-04-26" @default.
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- W4224252034 date "2022-07-01" @default.
- W4224252034 modified "2023-10-17" @default.
- W4224252034 title "Thalidomide-based Pt(IV) prodrugs designed to exert synergistic effect of immunomodulation and chemotherapy" @default.
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- W4224252034 doi "https://doi.org/10.1016/j.jinorgbio.2022.111842" @default.
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