JOURNAL ARTICLE

Radiosensitization of prostate cancer cells by the dual PI3K/mTOR inhibitor BEZ235 under normoxic and hypoxic conditions

Vincent A Potiron, Rym Abderrahmani, Rym Abderrhamani, Eric Giang, Sophie Chiavassa, Emmanuelle Di Tomaso, Sauveur-Michel Maira, François Paris, Stéphane Supiot
Radiotherapy and Oncology 2013, 106 (1): 138-46
23321494

BACKGROUND AND PURPOSE: Despite appropriate radiotherapy, high-risk prostate cancer patients often experience local relapse and progression to metastatic disease. Radioresistance may be due to tumor-hypoxia but also due to the PTEN mutation/deletion present in 70% prostate cancers. We investigated whether the novel PI3K/mTOR inhibitor BEZ235 might sensitize prostate cancer cells to radiation and reduce hypoxia-induced radioresistance.

MATERIALS AND METHODS: The potential radiosensitizing properties of BEZ235 were investigated in vitro and in vivo using two prostate cancer cell lines, PC3 (PTEN(-/-)) and DU145 (PTEN(+/+)), under normoxic (21% O(2)) and hypoxic (0.5% O(2)) conditions.

RESULTS: BEZ235 rapidly inhibited PI3K and mTOR signaling in a dose dependent manner and limited tumor cell proliferation and clonogenic survival in both cell lines independently of PTEN status. In vivo, BEZ235 pretreatment enhanced the efficacy of radiation therapy on PC3 xenograft tumors in mice without inducing intestinal radiotoxicity. In culture, BEZ235 radiosensitized both cell lines in a comparable manner. Moreover, BEZ235 inhibited PI3K/mTOR activation and radiosensitized both cell lines under normoxia and hypoxia. BEZ235 radiosensitizing effects correlated with a decrease in γH2AX foci repair and increased G2/M cell cycle arrest.

CONCLUSIONS: BEZ235 is a potent radiosensitizer of normoxic and hypoxic prostate cancer cells.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
23321494
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"