Knockdown of AURKA sensitizes the efficacy of radiation in human colorectal cancer.

AIMS

Abnormally amplified expression of AURKA (aurora kinase A) is closely related to chemo-resistance in human colorectal cancer, lung cancer and leukemia. However, the biological role of AURKA in response to radio-sensitivity in human colorectal cancer is still unknown. Therefore, we evaluated the radio-sensitize ability of perturbation AURKA in human colorectal cancer.

MAIN METHODS

The knockdown effect of shAURKA was determined by western blot and qRT-PCR, respectively. Cell growth was determined by CCK-8 and clonogenic assay. Cell migration and metastasis was measured by wound healing assay and transwell invasive assay, respectively. Cell cycle and apoptosis was analyzed by flow cytometry. The alteration of down-stream targets was determined by western blot analysis.

KEY FINDINGS

We observed that high-level of AURKA expression is associated with poor prognosis in CRC patients receiving radiotherapy. Knockdown of AURKA significantly sensitizes the efficacy of radiation on the proliferation of HCT116 and HT-29 cells. The combination of AURKA inhibition and radiation could effectively suppress the ability of cell migration and metastasis, but also synergistically induce cellular apoptosis and arrest cell cycle at G2/M phase. Further studies demonstrated that knockdown AURKA markedly enhanced the efficacy of radiation through elevated PARP cleavage and induced AURKA-mediated pro-apoptosis factor BIM. Meanwhile, knockdown of AURKA in combination with radiation synergistically suppressed the regulator in blockage of G2/M phase, CDK2.

SIGNIFICANCE

Taken together, our results provide the evidence that targeted inhibition of AURKA could be a promising strategy for enhancing the efficacy of radiation for the treatment of human colorectal cancer.