Inhibition of Aurora B by CCT137690 sensitizes colorectal cells to radiotherapy.

Abstract

Colorectal cancer is the third most commonly diagnosed cancer worldwide. Although surgery remains the best treatment for this disease, adjuvant chemotherapy and radiotherapy are also very important in clinical practice. However, the notorious refractory lack of responses to radiochemotherapy greatly limits the application of radiochemotherapy in the context of colorectal cancer.There is a growing interest in the role that Aurora B may play in colorectal cancer cell survival as well as other cancer subtypes. In the current study, we sought to ascertain whether blocking of Aurora B signaling machinery by a small molecule inhibitor, CCT137690, could synergize radiation-induced colorectal cancer cell death. Results showed that CCT137690 increases the sensitivity of SW620 cells to radiation. Mechanistic studies revealed that Aurora B-Survivin pathway may be involved in this synergistic effect.Taken together, our results for the first time show that Aurora B inhibition and radiation exert a synergistic effect, resulting in enhanced colorectal cancer cell death. This synergistic effect is clinically relevant as lower doses of radiation could be used for cancer treatment, and could provide significant clinical benefits in terms of colorectal cancer management, while reducing unwanted side-effects.

• Authors: Xiaoyu Wu, Wentao Liu, Qinhong Cao, Che Chen, Zhiwei Chen, Zhe Xu, Weisu Li, Fukun Liu, Xuequan Yao
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 33 Pg. 13 (Jan 29 2014) ISSN: 1756-9966 [Electronic] England
• PMID: 24476310 (Publication Type: Journal Article)

Chemical References

• 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo(4,5-b)pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole
• Imidazoles
• Pyridines
• AURKB protein, human
• Aurora Kinase B

Topics

• Aurora Kinase B (antagonists & inhibitors, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival (drug effects, radiation effects)
• Colorectal Neoplasms
• Humans
• Imidazoles (pharmacology)
• Inhibitory Concentration 50
• Pyridines (pharmacology)
• Radiation Tolerance (drug effects)