Basic & Clinical Cancer Research (Sep 2012)
Assessment and modulation of chemoresistance by different sub-groups of chemosensitizers in a NHL cell line model
Abstract
Background: The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as Non-Hodgkin’s Lymphoma (NHL). With the recognition of important roles for both p53 and its more recently described paralog p73 in mediating the activity of anti-cancer drugs, there has been increasing recognition that cellular resistance to anthracyclines could and does arise through failure of p53 family member signalling. Despite these advances in understanding how cells respond to DNA damage in vitro, and how this is affected by molecular genetic changes which affect p53 family member signalling, the contribution of these to in vivo chemoresistance has not been definitively established. Our major task now is to determine how these changes operate individually and collectively in vivo to produce the phenotype of clinical chemoresistance, and how we can translate this knowledge into clinically useful strategies to improve the outcome of chemotherapy. Materials and Methods: In this study we used two cell lines derived from Nigerian patients with Burkitt's lymphoma in a suspension type cell culture. The reduction of the tetrazolium salt to a blue-black formazan product by living not by dead cells can be used to measure growth inhibitory effects (cell proliferation inhibitory) of tumor cells. Results: An alternative option for p53+ (resistant) cells is to use a PGP reversal agent in combination with DOX, but reducing the dose of DOX when combined with chemosensitizer. Conclusion: The altered cellular dose in chemoresistant cell lines may provide a rational basis for the use of modified anthracycline based regimens in chemosensitizers, preferably non-genotoxic, in the treatment of tumors expressing chemoresistance phenotype with p53 over-expression.
