Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis
Abstract
Radiotherapy is a common therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to proliferate under genotoxic stress. The goal of this project is to determine whether silencing of MEK5 will sensitize prostate cancer cells to ionizing radiation. Previously, we showed that depletion of MEK5 sensitizes prostate cancer cells to gamma-radiation as determined by both clonogenic survival and cell proliferation assays. Furthermore, MEK5 silencing impairs phosphorylation of DNA-PKcs in response to IR, delays resolution of IR-induced gammaH2AX and 53BP1 foci, and reduces DNA repair by non-homologous end-joining. In the current funding period, we have extended our in vitro findings by conducting in vivo experiments. We show that MEK5 knockdown in PC3 human prostate cancer cells combined with x-ray irradiation leads to a significant reduction in tumor growth in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2018
- Accession Number
- AD1094311
Entities
People
- Constantinos G Broustas
Organizations
- Columbia University