In vivo Radiosensitization Effect of HDAC Inhibitor, SK-7041 on RIF-1 Cell Line / 대한방사선종양학회지

ABSTRACT

PURPOSE: To test the radiosensitizing effect of the newly synthesized novel histone deacetylase inhibitor, SK-7041 in vivo. MATERIALS AND METHODS: The RIF-1 cell line was implanted into the back of a 6-week-old female C3H mouse, intradermally. The mice were grouped into control, drug, radiation (RT), and RT+drug group. SK-7041, 4 mg/kg was administered intraperitoneally for six cycles every 12 hours for mice in the drug and RT+drug group. An identical volume of phosphate buffered saline (PBS) was administered at the same frequency to mice in the control and RT groups. A single 5 Gy fraction was delivered to mice in RT and RT+drug group 6 hours after the fourth delivery. The volume of the implanted tumor was measured every 2~3 days to formulate the growth delay curve. RESULTS: For the control, drug, RT, and RT+drug groups, the average duration for implanted tumor to reach a volume of 1,500 mm3 was 10 days, 10 days, 9 days, and 12 days, respectively. Moreover, the tumor volume on D14 was 276.7 mm3, 279.9 mm3, 292.5 mm3, and 185.5 mm3, respectively (p=0.0004). The difference for the change in slope for the control and drug versus the RT and RT+drug groups were borderline significant (p=0.0650). CONCLUSION: The results of this study indicate that SK-7041 has a radiosensitizing effect for the RIF-I cell line in vivo at a low concentration and this effect may be synergistic. Implementing this result to clinical trial is warranted.