Using zinc diethyldithiocarbamate (ZnDDC) to reverse hypoxia induced chemoresistance in multiple myeloma cell lines.

Using zinc diethyldithiocarbamate (ZnDDC) to reverse hypoxia induced chemoresistance in multiple myeloma cell lines.
February 6, 2021 No Comments Assignment Assignment help

Main aim of the project: To investigate the ability of ZnDDC to reverse hypoxia induced resistance to lenalidomide and pomalidomide in multiple myeloma cells. Background information: Multiple myeloma (MM) is an incurable malignant type of cancer which occurs in the plasma cells. Although the prognosis of different types of leukaemia has been significantly improved the outcomes of MM remain very poor. Even with new drugs such as pomalidomide and lenalidomide, MM remains challenging with a 10-year survival rate of 33% in the UK. The very high relapse rate and chemoresistance of MM could be attributed to the presence of MM cancer stem cells (MM-CSCs). The hypoxic microenvironment of the bone marrow provides a perfect niche for the maintenance and progression of the MM-CSCs through activation of the NF-kB pathway. Hence, drugs that target the CSCs and hypoxia induced NF-kB pathway could provide better clinical outcomes in the treatment of MM. Due to the time and costs for new drug development, repositioning of old drugs for new indications is an emerging drug R&D strategy in recent years. Disulfiram (DS), an anti-alcoholism drug used in clinic for over 60 years, demonstrates excellent activity against a wide range of cancers without toxicity to normal cells. The anticancer effect of DS is copper (Cu), zinc (Zn) and some other divalent transition metal elements dependent. The reaction of DS with Zn forms a stable complex ZnDDC which exerts its anticancer effect. Recently Prof. Wang’s group has developed a novel formulation of albumin conjugated ZnDDC. This study we will test the ability of ZnDDC to reverse hypoxia induced resistance to two first line anti-MM drugs lenalidomide and pomalidomide using MTT cytotoxicity assay.