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The α v β 3 integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of α v β 3 integrin on the radiosensitivity of prostate cancer cells and the molecular mechanism controlling cell survival in response to ionizing radiation (IR) was investigated. Both LNCaP cells stably transfected with α v β 3 integrin and PC-3 cells that contain endogenous β 3 integrin were used. This study demonstrated that α v β 3 integrin increases survival of α v β 3 -LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of α v β 3 integrin in PC-3 cells sensitizes to radiation. Expression of α v β 3 integrin in LNCaP cells also enhances anchorage-independent cell growth while knockdown of α v β 3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The α v β 3 antagonist, cRGD, significantly increases radiosensitivity in both α v β 3 -LNCaP and PC-3 cells. Moreover, α v β 3 integrin prevents radiation-induced downregulation of survivin. Inhibition of survivin expression by siRNA or shRNA enhances IR-induced inhibition of anchorage-independent cell growth. Overexpression of wild-type survivin in PC-3 cells treated with α v β 3 integrin shRNA increases survival of cells upon IR. These findings reveal that α v β 3 integrin promotes radioresistance and regulates survivin levels in response to IR. IMPLICATIONS: Future translational research on targeting α v β 3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.

αvβ3 Integrin Mediates Radioresistance of Prostate Cancer Cells through Regulation of Survivin