Cell-free DNA for the estimation of antitumor action of antitumor drug dioxadet in a model of disseminated ovarian cancer in rats

Tumor growth is characterized by a modified ratio of apoptotic and mitotic indexes. Cell-free DNA (cfDNA) is released into the circulation mainly as a result of apoptosis and correlates with the effectiveness of cytotoxic therapy.

Purpose of research was to assess the cfDNA levels change during tumor growth and the effect of antitumor drug from group of acetylated cytostatic dioxadet in a model of transplanted ascites ovarian cancer (OC) in female rats.

Tumor was transplanted intraperitoneally to 12-week-old Wistar rats (n=20) by introducing 1×10⁷ tumor cells in 0.5ml of saline. 48 h after OC inoculation dioxadet at the maximum tolerated dose of 1.5 mg/kg b.w. was injected intraperitoneally to rats (n=10) and saline was injected intraperitoneally to control rats (n=10). The results were evaluated by the increase in median survival (MS) of rats and by the content of cfDNA. Blood from rats was taken from the peripheral vein at intervals of 0, 2, 4, 6 and 8 days after inoculation and EDTA-plasma was separated. The cfDNA content was measured by ELISA assay.

The blood plasma cfDNA level of rats initially, before OC transplantation, was 1.6 ±0.33 ng/μl, without changing within 2 days, was significantly higher after 6 days (9.84±3.96 ng/μl, р<0.01) and remained elevated after 8 days. 2 days after the dioxadet administration the cfDNA level in the experimental group was lower than in the control group (0.78±0.33 vs 2.33±1.17 ng/μl, р<0.025), but 6 and 8 days after OC transplantation the cfDNA level did not differ significantly from the baseline. MS of rats treated with dioxadet was 46.0 days, control - 29.5 days (p=0.0049).

A significant (56%) increase in rat’s life expectancy caused by dioxadet is accompanied by cfDNA level decrease in the 2 days after injection of the drug. Thus, the measurement of сfDNA can be used to assess the effectiveness of the cytostatic effect in the clinic.