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• W3033378162 endingPage "192" @default.
• W3033378162 startingPage "178" @default.
• W3033378162 abstract "Abstract Aryl hydrocarbon receptor (AHR), a ligand‐activated transcription factor, is considered as a crucial gene during tumor formation and progress. Among various ligands, 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester (ITE) has been evaluated to share a broad spectrum of biological activities. However, the specific effects and potential mechanisms of ITE against hepatocellular carcinoma remain unclear. Here we explored whether ITE exerted antitumor activity against hepatocellular carcinoma (HCC) cells and its potential mechanisms in vitro and in vivo. We found that ITE could markedly inhibit proliferation of HCCLM3 and SMMC‐7721 cells and induce G0/G1 arrest and apoptosis with alterations of expressions of the related proteins. Also, ITE could prohibit the process of migration and invasion evaluated by transwell assay. Moreover, ITE exhibited remarkable capability to repress the growth of HCCLM3‐SR cells and induce apoptosis in contrast to sorafenib. Additionally, ITE also showed potent antitumor activity against the HCCLM3 xenograft by prohibiting tumor growth without any toxicity to mice. Mechanistically, AHR activation by ITE was attributed to inhibition of HCC cells as AHR knockdown would abolish ITE‐induced suppression in HCC cells, and overexpression of AHR would potentiate antitumor activity regulated by ITE. Our data suggested that ITE manifested a marked antitumor effect against HCC cells both in vitro and in vivo via AHR activation mainly through inducing G1/G0 arrest and apoptosis and inhibiting the process of migration and invasion. Furthermore, we also found the PI3K/AKT pathway was involved in sorafenib‐induced resistance and ITE could restore sensitivity by suppressing the PI3K/AKT pathway. Collectively, our study revealed that ITE would be a promising therapeutic agent to deal with HCC and an alternative for drug‐resistant HCC." @default.
• W3033378162 created "2020-06-12" @default.
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• W3033378162 date "2020-06-08" @default.
• W3033378162 modified "2023-10-14" @default.
• W3033378162 title "The aryl hydrocarbon receptor ligand ITE inhibits cell proliferation and migration and enhances sensitivity to drug‐resistance in hepatocellular carcinoma" @default.
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• W3033378162 doi "https://doi.org/10.1002/jcp.29832" @default.
• W3033378162 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32510618" @default.
• W3033378162 hasPublicationYear "2020" @default.
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