Chemosensitivity To Lidamycin In Cancer Cells Overexpressing HER2 And Mdr1

The HER2 gene is one of the most studied molecules in the field of cancer research. The HER2 gene encodes a 185-kDa transmembrane glycoprotein which belongs to the epidermal growth factor receptor family. The activated HER2 receptor can mediate the signal transduction of MAPK and PI3K/Akt pathways, which play a crucial role in cell growth, differentiation, and apoptosis. The HER2 gene is amplified and/or overexpressed in many types of human malignancies. Patients with overexpressed HER2 predict a reduced disease-free and overall survival, a poor clinical outcome. Overexpressing HER2 confers cancer cells increased resistance to various cancer therapies.Multidrug resistance (MDR) is one of the biggest obstacles to success in tumor chemotherapy. Overespressing of P-glycoprotein (P-gp) encoded by mdr1 gene is the classic mechanism of causing MDR. As an integral part of plasma membrane, P-gp acts as a drug efflux pump that actively extrudes drugs from tumor cells, thereby decreasing the concentration of chemotherapeutic agents in cancer cells.Lidamycin (LDM), an antibiotic produced by Streptomyces globisporus strain which was isolated in our lab, displayed extremely potent cytotoxicity against tumor cells.Plasmid pcDNA3.1/HER2 and pcDNA3.1/mdrl were conctructed, stably transfected breast cancer cell MCF-7/HER2 and hepatoma cancer cell HepG2/mdr1 was obtained respectively in this study. We explored the antitumor activity of Lidamycin on cancer cells overexpressing HER2 and mdrl gene.1. Chemosensitivity to Lidamycin in Cancer Cells Overexpressing HER2Using plasmid pcDNA3.1/HER2 and control plasmid we obtained transfected...