Regorafenib suppresses epidermal growth factor receptor signaling-modulated progression of colorectal cancer.

Regorafenib suppresses epidermal growth factor receptor signaling-modulated progression of colorectal cancer. Biomed Pharmacother. 2020 Jun 02;128:110319 Authors: Liu YC, Tsai JJ, Weng YS, Hsu FT Abstract Active epidermal growth factor receptors (EGFR) signaling mediates the progression of colorectal cancer (CRC) through activation of downstream kinases and transcription factors. The increased expression of EGFR was associated with worse prognosis in patients with metastatic CRC (mCRC). Regorafenib, the oral kinase inhibitor approved for the treatment of mCRC, has been shown to reduce activation of downstream kinases of EGFR signal pathway in hepatocellular carcinoma and osteosarcoma. However, whether EGFR inactivation was participates in regorafenib-inhibited progression of CRC still remaining ambiguous. The major purpose of present study was to verify effect of regorafenib on EGFR signaling-mediated progression of CRC. Here, we investigated the effect of regorafenib or erlotinib (EGFR inhibitor) on tumor cell growth, invasion ability, apoptotic, and EGFR signal transduction in CRC in vitro and in vivo. Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Both regorafenib and erlotinib significantly reduced cell invasion ability, activation of protein kinase C-δ (PKCδ), protein kinase B (AKT), extracellular signal-regulated kinases (ERK),...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research