Hypoxia Response Elements Can Cause the Overexpression of the BAX mRNA Under Hypoxic Condition

Abstract

Background: Suicide gene therapy is one of the modern methods of cancer treatment. However, transmission for tumor cells is one of the main challenges to overcome. Hypoxia is a common phenomenon in solid tumors that lead to changes in tumors microenvironment. Hypoxia-responsive element sequences are regulatory sequences that lead to activation of their upstream and downstream genes in hypoxic time. Bax is a strong proapoptotic gene that causes apoptosis in the time of over expression in cells. Objectives: The aim of this study is to use this sequence in order to specify suicide gene therapy by the help of a gene producing Bax protein under control of CMV promoter. Methods: The gene of BAX, BAX3HRE and 3HRE were cloned into interested vectors. In the next step, the function of HRE sequence on over expression of upstream gene under hypoxic condition was evaluated through western blot, MTT assay and real time PCR. Results: The results of this study indicate that cells transected by pcDNA3.1/BAX 3HRE. The rate of apoptosis in them significantly increased in comparison with pcDNA3.1/BAX in hypoxic conditions. Conclusions: Regarding the role of HREs in increasing the expression of its upstream genes, it can be used to specify suicide gene therapy in treatment of solid tumors.