Combination of integrin siRNA and irradiation for breast cancer therapy

Abstract: Up-regulation of integrin αvβ3 has been shown to play a key role in tumor angiogenesis and metastasis. In this study, we evaluated the role of integrin αvβ3 in breast cancer cell resistance to ionizing irradiation (IR) and tested the anti-tumor efficacy of combining integrin αv siRNA and IR. Colonogenic survival assay, cell proliferation, apoptosis, and cell cycle analysis were carried out to determine the treatment effect of siRNA, IR, or combination of both on MDA-MB-435 cells (integrin αvβ3-positive). Integrin αvβ3-negative MCF-7 cells exert more radiosensitivity than MDA-MB-435 cells. IR up-regulates integrin αvβ3 expression in MDA-MB-435 cells and integrin αv siRNA can effectively reduce both αv and αvβ3 integrin expression, leading to increased radiosensitivity. Integrin αv siRNA also promotes IR-induced apoptosis and enhances IR-induced G2/M arrest in cell cycle progression. This study, with further optimization, may provide a simple and highly efficient treatment strategy for breast cancer as well as other integrin αvβ3-positive cancer types. [Copyright &y& Elsevier]