Mechanisms of Radiosensitization by the Neurotensin Receptor Antagonist SR48692 in Prostate Cancer Models

摘要

This project tests the hypothesis that blocking NTR1 receptor with antagonist SR48692 could selectively sensitize prostate cancer cells to ionizing radiation, thus improving outcomes of radiotherapy. In this second year period, we studied the molecular mechanism of radiosensitization using several prostate cancer cell lines differing in the expression levels of NTR1 receptor, EGFR receptor and androgen receptor (AR). We demonstrated that SR48692 selectively sensitizes prostate cancer cells but not normal epithelial cells, due to differences in NTR1 expression. We also demonstrated that the level of radiosensitization depends on EGFR expression in cells. However, sensitization does not depend on AR expression, suggesting that SR48692 treatment could be used to enhance radiotherapy of both androgen-dependent and independent tumors.