Vaccinating the UK against covid-19
Azeem Majeed, Mariam Molokhia
Abstract
Background: Heterodimer cooperation between ErbB receptors has limited clinical usefulness of receptor tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib in the treatment of cancer. However, combination treatment of TKIs with γ-tocotrienol targets multiple ErbB receptors and significantly inhibit +SA murine mammary tumor cell growth. Materials and Methods: Cell proliferation was determined by tetrazolium (MTT) assay and immunofluorescent Ki-67 staining. Western blot analysis was used to determine treatment effects on epidermal growth factor (EGF)-dependent mitogenic signaling. Results: Combined treatment of 3 μM γ-tocotrienol with 0.25 μM erlotinib or 0.5 μM gefitinib significantly inhibited +SA cell growth and reduced cyclin D1 and phosphorylated (active) Pdk-1, Akt, Stat3 and Stat5 levels. Conclusion: Combined treatment of γ-tocotrienol with erlotinib or gefitinib prevents ErbB receptor heterodimer cooperation and inhibits EGF-dependent mitogenic signaling in +SA murine mammary tumor cells. These findings strongly suggest that combination treatment may significantly improve therapeutic responsiveness in breast cancer patients.