RESUMEN
The αvß3 integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of αvß3 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 αvß3 integrin and PC-3 cells that contain endogenous ß3 integrin were used. This study demonstrated that αvß3 integrin increases survival of αvß3-LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of αvß3 integrin in PC-3 cells sensitizes to radiation. Expression of αvß3 integrin in LNCaP cells also enhances anchorage-independent cell growth while knockdown of αvß3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The αvß3 antagonist, cRGD, significantly increases radiosensitivity in both αvß3-LNCaP and PC-3 cells. Moreover, αvß3 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 αvß3 integrin shRNA increases survival of cells upon IR. These findings reveal that αvß3 integrin promotes radioresistance and regulates survivin levels in response to IR. IMPLICATIONS: Future translational research on targeting αvß3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.