Abstract
Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.
Keywords:
AGR2; autophagy; etravirine; ovarian cancer.
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Drug Synergism
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Mice
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Mucoproteins / genetics
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Mucoproteins / metabolism*
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Neoplasm Metastasis
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Nitriles / administration & dosage*
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Nitriles / pharmacology
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism
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Paclitaxel / administration & dosage*
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Paclitaxel / pharmacology
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Proteolysis
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Pyrimidines / administration & dosage*
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Pyrimidines / pharmacology
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Reverse Transcriptase Inhibitors / administration & dosage*
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Reverse Transcriptase Inhibitors / pharmacology
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Xenograft Model Antitumor Assays
Substances
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AGR2 protein, human
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Mucoproteins
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Nitriles
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Oncogene Proteins
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Pyrimidines
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Reverse Transcriptase Inhibitors
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etravirine
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Paclitaxel