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• W2804433419 abstract "Chemotherapy resistance represents a major obstacle in the treatment of patients with hepatocellular carcinoma (HCC). The purpose of this study was to investigate the anti-cancer effect of MEL-pep, a novel analog of the natural antibacterial peptide melittin (MEL), on human 5-fluorouracil-resistant HCC cells (BEL-7402/5-FU) and to clarify the molecular mechanisms involved in these effects. We found that MEL-pep inhibited the proliferation of BEL-7402/5-FU cells and reversed 5-FU resistance in vitro. MEL-pep directly bound to BEL-7402/5-FU cells and disrupted the cell membrane. P-glycoprotein (P-gp) plays an important role in the development of resistance to anticancer drugs. We found that MEL-pep inhibited P-gp expression and increased the intracellular accumulation of the P-gp substrate rhodamine-123 in BEL-7402/5-FU cells. Additionally, the phosphorylation of Akt and NF-κB/p65 nuclear translocation was all inhibited by MEL-pep. Insulin ­ like growth factor I, a phosphatidylinositol 3 kinase(PI3K) /protein kinase B(AKT) agonist, reversed MEL-pep induced P-gp suppression. Therefore, MEL-pep inhibited P-gp expression by deactivating the PI3K/Akt signaling pathway. Finally, in a BEL-7402/5-FU cell-derived xenograft tumor model in mice, we found that the intratumoral administration of MEL-pep inhibited tumor growth in a dose-dependent manner. Thus, MEL-pep could be a promising candidate in the treatment of chemotherapy resistant HCC." @default.
• W2804433419 created "2018-06-01" @default.
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• W2804433419 date "2018-08-01" @default.
• W2804433419 modified "2023-10-15" @default.
• W2804433419 title "MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells" @default.
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• W2804433419 doi "https://doi.org/10.1016/j.biocel.2018.05.013" @default.
• W2804433419 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29800725" @default.
• W2804433419 hasPublicationYear "2018" @default.
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