Lipoxygenase, Angiogenicity, and Prostate Cancer Radioresistance
Annual rept. 1 Jan-31 Dec 2005
SOUTHERN ILLINOIS UNIV SCHOOL OF MEDICINE SPRINGFIELD
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Radiotherapy is a prevalent modality for the treatment of prostate tumor. Although radiation is capable of eradicating localized prostate tumors, nearly 30 of patients treated with potentially curative doses relapse at the sites of irradiation. Therefore, there is an imperative need to improve the success rate of radiotherapy for PCa. This proposal is focused on a role of 12-lipoxygenase LOX in modulating the radiation response of PCa cells. 12-LOX catalyzes the formation of 12S-hydroxyeicosatetraenoic acid HETE. Our studies suggest an involvement of 12-LOX in radioresistance of PCa cells. It is our hypothesis that an increase in 12-LOX expressionactivity may lead to an increased resistance in tumors to radiation treatment. We also hypothesize that VEGF is an important intermediary for 12-LOX mediated radioresistance in PCa. We intend to define the role of 12-LOX in radioresponse in PCa. 12-LOX will be overexpressed in LNCaP and DU145 cells. Then we will study whether an increase in 12-LOX expression in LNCaP and DU145 cells can enhance their resistance to radiotherapy. We also propose to study whether VEGF is required by 12-LOX to enhance PCa radioresistance through blockade of VEGF activity with a neutralizing antibody. Finally, we will evaluate whether BHPP, a 12-LOX inhibitor, can be used to sensitize prostate tumors to radiotherapy.
- Medicine and Medical Research