Abstract
Heavy particle radiotherapy is a useful means to eradicate solid tumors because of its physical, chemical and biological properties. It is, however, needed to accumulate the more evidence for the combined therapy between heavy particles and chemical agents for overcoming intractable tumors. In this study, we investigate a combination effect of carbon-ion irradiation and the telomerase inhibitor MST-312 treatment in tumor cells. Human cervical cancer HeLa cells were used here. Firstly, cells were cultured for 24 h at various concentrations of MST-312. After treatment, cells were reseeded in fresh medium without MST-312. Colonies having more than 50 cells were counted at day 14 to determine the survival. The survival decreased with increasing MST-312 concentration and cells could not form any colonies at 5 μM or higher concentration. Secondly, cells were cultured for 24 h with or without 1 μM MST-312, and then, irradiated with carbon ions (LET=110 keV/μm) and gamma-rays to evaluate the combined effect of irradiation and MST-312 treatment. After irradiation, cells were reseeded in fresh medium without MST-312 and colonies were counted as described above. The survival of the irradiated cells additively decreased in combination with MST-312 treatment. Irradiation and MST-312 treatment might inactivate the clonogenic potential of tumor cells through independent mechanisms. The doses needed to reduce the survival of irradiated cells to 10% were decreased by MST-312 treatment from 1.2 Gy to 0.5 Gy (carbon-ion irradiation) and from 5.4 Gy to 4.0 Gy (gamma-ray irradiation), respectively. MST-312 pre-treatment may reduce the dose needed for a curative effect in heavy-particle radiotherapy.
