Antitumor activity of tropolone JO-122(2) in subcutaneous CDX models of cancer

Purpose of the study. The present study investigates the antitumour effect of tropolone 2-(1,1‑dimethyl‑1H-benzo[e]indolin‑2‑yl)-5,6,7‑trichloro‑1,3‑tropolone (JO‑122(2)) in monotherapy and in combination with fluorouracil in subcutaneous CDX models of gastric cancer. Materials and methods. The experimental work was conducted on female BALB/c Nude mice (n = 32), with ages ranging from 6 to 8 weeks. The CDX models were created by subcutaneous administration of a tumor culture of human gastric adenocarcinoma (AGS) in a dose of 5 × 106 cells per mouse. After the tumors reaching a volume of 70–100 mm³, the animals were divided into four groups of eight individuals each, with the objective of ensuring minimal variation in the mean tumor node volume between groups. The efficacy of the therapeutic intervention was evaluated by measuring the inhibition of tumor growth (TGI %). The statistical data processing was performed using the Microsoft Excel 2013 and STATISTICA 12 software packages. The Mann–Whitney U test was utilized to evaluate the disparities between the experimental and control groups. Differences were considered statistically significant at p < 0.05. Results. Consequently, subcutaneous CDX models of gastric adenocarcinoma were obtained. The study demonstrated that the administration of JO‑122(2) as a monotherapy did not result in a statistically significant impact on the growth of tumor nodes. The most significant antitumor activity was observed in the group administered combination therapy (JO‑122(2) + 5‑fluorouracil). The mean value of tumor node volumes at the conclusion of the experiment (on day 29 after the commencement of treatment) in this group was 513.98 ± 56.50 mm³, whereas in the control group it was 915.08 ± 49.93 mm³. A comparison of tumor growth rates between the groups receiving 5‑fluorouracil monotherapy and combination therapy revealed statistically significant differences as early as the 22nd day of the experiment. Furthermore, the highest TPO value was observed in the group administered the combination of drugs, at 43.83 %. Conclusion. The results demonstrated a more effective antitumor effect on gastric adenocarcinoma models when tropolone was used in combination with a cytostatic. This finding suggests the potential for further investigation into the properties of this compound and the possibility of extending its study.