Tumor suppressor BaxΔ2 is a functional Bax isoform that is found in microsatellite unstable (MSI) colon cancer. However, BaxΔ2 proteins are... Show moreTumor suppressor BaxΔ2 is a functional Bax isoform that is found in microsatellite unstable (MSI) colon cancer. However, BaxΔ2 proteins are not stable and are prone to be degraded by proteasomes in tumor cells. Bortezomib, a proteasome inhibitor, is an FDA approved anti-cancer drug mainly used for the treatment of myeloma and lymphoma. We tested if Bortezomib can block BaxΔ2 degradation and potentially be beneficial for the treatment of BaxΔ2 positive colon cancer. In this project, we compared the efficacy of Bortezomib-induced cell death in BaxΔ2-positive and BaxΔ2-negative colon cancer cells. We found that BaxΔ2-positive cells were highly sensitive to Bortezomib-induced cell death in comparison with that in BaxΔ2-negative cells. The half maximal inhibitory concentration (IC50) of cell viability for BaxΔ2-positive cells is 11.1 nM, while it is 453.8 nM for BaxΔ2-negative cells. The results indicate that Bortezomib has a selectivity towards BaxΔ2-expressive cells and could be a drug candidate for the treatment of BaxΔ2-positive colon cancer. M.S. in Biology, May 2015 Show less
