Antitumor effectiveness of combination therapy with platinum and hybrid organotin compound on the Lewis epidermoid carcinoma model with metronomic administration.

Abstract

e15080 Background: The prevalence of lung malignancies in Russia in 2019 was 100.5 per 100,000 population, which is 2.5% more than in the previous year. Drug therapy remains one of the main methods of treatment of malignant lung neoplasms. An urgent task for specialists in experimental pharmacology and oncology is searching for new antitumor compounds. Hybrid organotin compound (3,5-di-tert-butyl-4-hydroxyphenylthiolate)triphenylol) is a promising candidate for antitumor drugs [Milaeva E.R. et al. Novel selective anticancer agents based on Sn and Au complexes. Pure & Applied Chemistry. 2020, 92, 1201-1216]. The combined administration of platinum antitumor drug and an organotin compound will increase the effectiveness of therapy and reduce the general toxic effect on the body. Methods: The study was conducted on C57bl/6 mice (females, n = 48, each cohort contained 12 mice) on the Lewis epidermoid carcinoma model (subcutaneous transplantation) [Frantsiants E.M. et al. Method for Stimulation of Malignant Growth by Chronic Pain in Rat Lungs. Bulletin of Experimental Biology and Medicine. 2020, 169(2), 290–292]. Cisplatin-Teva (CP) and (3,5–di–tert–butyl–4–hydroxyphenylthiolate)triphenylolol) (Me-5) were used as chemotherapeutic agents. Groups of animals were formed as follows: I (experimental) - CP at a dose of 1 mg/kg + Me-5 at a dose of 25 mg/kg; II (comparison group) - CP at a dose of 1 mg/kg; III (comparison) - Me-5 at a dose of 25 mg/kg; IV (control group) - without pharmacological substances. All manipulations were carried out according to the European Convention for ETS 123. The compounds were administered intraperitoneally daily during 10 days. 21 days after the subinoculation of tumor cells all animals were euthanized. The antitumor effect was estimated by the percentage inhibition of tumor growth by weight. Results: The combination of the studied substances has a more pronounced antitumor effect. The percentage of reduction in the mass of the primary focus in group I was 38.1%, in group II - 20.4%, in group III - 12%. The obtained results showed that the percentage of inhibition of tumor growth by weight with a tenfold combined administration of Cisplatin-Teva and Me-5 on the Lewis epidermoid carcinoma model was significantly higher than the previously obtained result when studying the combination of Cisplatin-Teva and Me-5 with a five-fold administration [Dodokhova M.A. et al. Effect of cisplatin and hybrid organotin compound in low doses on the growth and metastasis of lewis epidermoid carcinoma in experiment. Eksperimental'naya i Klinicheskaya Farmakologiya. 2021, 84(8), 32–35], which is 38.1% and 25%, respectively. Conclusions: The research suggests a multifactorial mechanism of action of hybrid organotin compounds.