401 ORAL APOCYNIN SENSITIZES PROSTATE CANCER XENOGRAFTS TO RADIATION

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011401 ORAL APOCYNIN SENSITIZES PROSTATE CANCER XENOGRAFTS TO RADIATION Alex Wolf, Doug Boreham, and Jehonathan Pinthus Alex WolfAlex Wolf Hamilton, Canada More articles by this author , Doug BorehamDoug Boreham Hamilton, Canada More articles by this author , and Jehonathan PinthusJehonathan Pinthus Hamilton, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.490AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiation therapy (RT) is a well established therapy for prostate cancer (PC), but treatment failure occurs in 45% of patients. We have previously shown that the basal levels reactive oxygen species (bROS) in PC cells negatively correlate with their radiosensitivity, and that Apocynin, an NADPH oxidase (NOX) inhibitor can sensitize in-vitro PC cells to radiation by lowering their bROS levels. The primary objective of this study was to take these observations a step forwards and verify it in-vivo. The second objective was to determine the optimal timing of anti-oxidative therapy which will not interfere with the therapeutic effect of RT that is based itself on the induction of acute oxidative attack. The third objective was to test if apocynin can sensitize non-cancerous neighboring tissue (skin) to radiation and thus increase toxicity of RT. METHODS MATLyLu (rat PC cell line) served as a model because it is a very aggressive PC model for which RT (10Gy given at 2Gy/day) can delay progression but is not curative. Thus, related experimental manipulation can result in a readable response. N=98 male Copenhagen rats were implanted s.c with MATLyLu cells. When tumours reached 5mm diameter rats were divided into 5 groups: N=19 received no treatment (control), n=21 received 5mM Apocynin in drinking water x 14 days with no RT, n=20 received RT only, n=18 received 5mM Apocynin in drinking water followed by RT and n=20 received 5mM Apocynin in drinking water 5 days before RT, 5 days during RT and 4 days after RT. Rats were followed for survival and were euthanized if tumours reached a diameter>35mm, had skin ulceration over the tumor or were ill. Kaplan Meyer curves were constructed and the differences in survival between the different groups were calculated by the log-rank test. RESULTS Control untreated rats and rats receiving apocynin only had the same minimal survival (median survival of 19 and 20.9 days respectively). RT significantly extended survival (median survival time of 34.3 days p<0.0001). Survival was significantly increased in rats which received apocynin orally throughout a course of radiotherapy (p=0.0418), but not if it was discontinued before radiotherapy (p=0.208). Apocynin did not sensitize normal surrounding skin to radiation (p=0.185). CONCLUSIONS 1. Apocynin promotes the in-vivo response of PC to RT without toxic effects on neighbouring normal tissues 2. Manipulating the oxidative capacity of PC sensitized it to RT only when applied concomitantly with the radiation. This may suggest that patients who take commonly used anti-oxidants vitamins may not have to cease it during RT. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e162 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alex Wolf Hamilton, Canada More articles by this author Doug Boreham Hamilton, Canada More articles by this author Jehonathan Pinthus Hamilton, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...