Fig. 5

In vivo anti-tumor effects of OR-2003 and OR-2100. a Timing and duration of the treatment. HCT116 cells were subcutaneously injected into nude mice, and once tumors reached an average volume of 80 mm³, mice were treated by intraperitoneal injection of vehicle, DAC, OR-2003, or OR-2100 twice per week. The mice in group 1 and group 2 were treated with drugs for 22 days and 11 days, respectively. b Changes in tumor volumes. The tumor volume was measured twice per week for mice in group 1. DAC (0.625 and 1.250 mg/kg) suppressed the xenograft growth, but dose dependence was unclear. Both OR-2003 and OR-2100 demonstrated significant and dose-dependent inhibition of tumor growth. c DNA demethylation in xenograft tumors. The effect of OR-2003 and OR-2100 on DNA demethylation was analyzed using xenograft tumors of mice in group 2. OR-2003 and OR-2100 induced significant demethylation in vivo comparable to DAC although the level was small. Values show mean ± SD of three experiments. d Body weight changes of mice in the three groups. There was no significant difference in the severity of body weight loss at the time of sacrifice among the three groups. Results are shown as mean ± SD. e Adverse-effects observed in the blood tests. A decrease in WBC counts and impairment of the liver function was observed in the group treated with DAC. On the other hand, OR-2003 and OR-2100 at concentrations equimolar to DAC exhibited no adverse effects on WBC counts and liver function. Results are shown as mean ± SD (n = 5 or 6/group)