|Title:||Varlitinib downregulates HER/ERK signaling and induces apoptosis in triple negative breast cancer cells||Authors:||Liu C.-Y.
|Keywords:||pan-HER inhibitor; Triple-negative breast cancer||Issue Date:||2019||Publisher:||MDPI AG||Journal Volume:||11||Journal Issue:||1||Source:||Cancers||Abstract:||
Triple-negative breast cancer (TNBC) is a complex disease associated with the aggressive phenotype and poor prognosis. TNBC harbors heterogeneous molecular subtypes with no approved specific targeted therapy. It has been reported that HER receptors are overexpressed in breast cancer including TNBC. In this study, we evaluated the efficacy of varlitinib, a reversible small molecule pan-HER inhibitor in TNBC. Our results showed that varlitinib reduced cell viability and induced cell apoptosis in most TNBC cell lines but not in MDA-MB-231 cells. MEK and ERK inhibition overcame resistance to varlitinib in MDA-MB-231 cells. Varlitinib inhibited HER signaling which led to inhibition of migration, invasion and mammosphere formation of TNBC cells as well as significant suppression of tumor growth of MDA-MB-468 xenograft mouse model. In summary, these results suggest that HER signaling plays an important role in TNBC progression and that pan-HER inhibition is potentially an effective treatment for TNBC patients. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
|ISSN:||2072-6694||DOI:||10.3390/cancers11010105||SDG/Keyword:||epidermal growth factor receptor; mitogen activated protein kinase; varlitinib; animal cell; animal experiment; animal model; antineoplastic activity; antiproliferative activity; apoptosis; Article; cancer cell; cancer growth; cell invasion; cell migration; cell viability; controlled study; diarrhea; down regulation; drug efficacy; drug inhibition; drug resistance; drug screening; enzyme inhibition; female; human; human cell; in vitro study; in vivo study; MDA-MB-231 cell line; mouse; nonhuman; signal transduction; triple negative breast cancer; tumor xenograft
|Appears in Collections:||基因體暨蛋白體醫學研究所|
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