Proteomic analysis of mitochondrial proteins in doxorubicin-resistant cancer cells

Abstract

Human uterine cancer occurs most often in menopause women between the ages of 55 and 70 years. In the initial stage, the symptoms of uterus have an abnormal vaginal bleeding or abnormal discharge, and the common treatment is to remove the uterus or treat with chemotherapeutic drugs. For most type of cancers, doxorubicin is frequently prescribed for treating a wide range of various types of cancers, including hematologic malignancies, lymphoma, myeloma, sarcoma, and uterine cancer. However, most cancer cells will become drug insensitivity or resistance via unknown mechanisms. Since mitochondria play a crucial role in the induction apoptosis, it is intriguing to clarify whether doxorubicin-resistance is mediated through mitochondrial protection. In this study, a highly doxorubicin-resistant cell line has been established by continuously culturing the MES-SA/Dx5, a commercial doxorubicin-resistant human uterine cancer cell line, in the presence of doxorubicin for up to 2 years. Mitochondrial proteins from nondrug-resistant MES-SA, low resistant MES-SA/Dx5 (MES-SA/Dx5low), and high resistant MES-SA/Dx5 (MES-SA/Dx5high) were enriched, and mitochondrial proteome is characterized by two dimensional-differential gel electrophoresis and matrix-assisted laser desorption/ ionization time of flight mass spectrometer (MALDI-TOF MS).