In light of this notion, we started to search for poten tial sensitization targets for radiotherapy of CRC subjects and we found that there is a recent growing interest in the role of Aurora B and cancer biology. In terms of synergistic effect of Aurora B inhibition and radiotherapy sensitivity, a previous study has shown that Aurora B inactivation sensitizes mesothelioma cells. In addition, Aurora B inhibition also potently sup presses repopulation during fractionated irradiation of human lung cancer cells. In the current study, we first show that SW 620 colorec tal cancer cells are relatively resistant to Aurora B inhibition by CCT137690 and to radiation. How ever, we found that the combination of Aurora B inhib ition and radiation exerts synergistic effects on cancer cell growth inhibition.

Our results showed that low dose radi ation greatly exaggerates the growth inhibitory ef fect of CCT137690 on SW 620 cells, as well as a low dose of CCT137690 dramatically increases the sensitivity of cells to radiation. Our observations provide a good proof of concept that both chemotherapy and radiotherapy doses could be greatly lowered by taking selleckchem Oxiracetam the advantages of synergistic effects of those two interventions. This could be trans lated into the clinic where the expectation is that there would be less adverse side effects and better patient tolerance at lower doses. These findings are especially important given that CT137690 has a narrow safety margin. In terms of understanding of the mechanism by which inhibiting Aurora B increases radiosensitivity of CRC cells, we found that Aurora B survivin pathway may be involved.

you can check here These findings are consistent with several reports showing the association of Aurora B and survivin in context of CRC. For example, Tuncel et al. reported that nuclear Aurora B and cytoplasmic survivin expression is involved in lymph node metastasis of colo rectal cancer. Moreover, Aurora survivin signaling machinery has been implicated in other cancers such as myelodysplasia, chronic lymphocytic leukemia, head and neck squamous cell cancer. In this regard, we observed that forced expression of survivin dramatic ally ameliorates Aurora B inhibition induced CRC cell death in the context of radiation. Taken together, our results for the first time showed that Aurora B inhibition, via CCT137690, and radiation exposure may play synergistic effects in colorectal cancer death. Taking advantage of this synergistic effect, a lower dose of radiation exposure and or chemical exposure is required for cancer cell death induction, which may have significant clinical implications for CRC management. Introduction Pharmacological cancer therapy for decades was per formed with non targeted mostly DNA interacting cytostatic drugs.