Abstract
Potential advantage of greater biological effectiveness and excellent dose distribution over low-LET radiations represents the rational for the clinical usage of high-LET heavy ions, which are shown to effectively overcome the radioresitance of tumor cells. It has recently been reported that HA14-1, an inhibitor of Bcl-2, sensitizes radioresistant tumor cells, which overespress Bcl-2, to low-LET radiations. In this study, we tested whether HA14-1 exacerbates heavy ion-induced killing of Bcl-2 overexpressing tumor cells. In the absence of HA14-1, HeLa cells which overexpress Bcl-2 (HeLa/bcl-2) were more resistant to cobalt-60 gamma-rays than the cells which express only neomycin resistant gene (HeLa/neo), but the sensitivity of HeLa/bcl-2 cells to carbon ions (108 keV/μm) was comparable to that of HeLa/neo cells. Interestingly, our preliminary data show that treatment with HA14-1 1 hr prior to carbon ion irradiation sensitized both cells, such that HeLa/neo cells were sensitized more dramatically than HeLa/bcl-2 cells. This result suggests that HA14-1 enhances the killing effect of heavy ions in tumor cells in a manner that depends on the expression level of Bcl-2.
