αβ Integrin Mediates Radioresistance of Prostate Cancer Cells through Regulation of Survivin.

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