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- W3136784282 abstract "TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspase-8, HSP60, and p53. These results demonstrate the effectiveness of AD-O51.4 protein in CRC preclinical models and identify the potential mechanism underlying acquired resistance. Progression of AD-O51.4 to clinical trials is expected." @default.
- W3136784282 created "2021-03-29" @default.
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- W3136784282 date "2021-03-19" @default.
- W3136784282 modified "2023-10-17" @default.
- W3136784282 title "Cytotoxic Efficacy and Resistance Mechanism of a TRAIL and VEGFA-Peptide Fusion Protein in Colorectal Cancer Models" @default.
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- W3136784282 doi "https://doi.org/10.3390/ijms22063160" @default.
- W3136784282 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8003782" @default.
- W3136784282 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33808900" @default.
- W3136784282 hasPublicationYear "2021" @default.
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