Methodological aspects for preclinical evaluation of antitumor activity on the example of an original cytostatic agent in Wistar rats with transplanted carcinosarcoma Walker 256

Ya.G. Murazov, ORCID 0000-0002-6573-3112
A.N. Stukov, ORCID 0000-0002-1741-6630
Iu.G. Zmitrichenko, ORCID 0000-0002-9137-9532
G.V. Tochilnikov, ORCID 0000-0003-4232-8170

N.N. Petrov National Medical Research Center of Oncology of the Ministry of Healthcare of the Russian Federation

E-mail: yaroslav84@yandex.ru

Abstract

The article presents the main quantitative indicators used for the preclinical evaluation of the pharmacological activity of promising anticancer drugs. As an example, the results of a study of the therapeutic activity of the domestic cytostatic compound chlonisol presented on a model of a transplanted allograft strain (carcinosarcoma Walker 256) in Wistar rats. After subcutaneous transplantation into the thigh of 0,5 ml of 10% suspension of tumor cells in normal saline, 25 mature male Wistar rats were randomized into two groups: 1st Control (n=15) – rats were injected intraperitoneally with 0,5 ml of normal saline; 2nd Chlonisol (n=10) – the animals injected intraperitoneally with the test compound at a dose of 15 mg/kg (75% of the maximum tolerated dose) in normal saline. The treatment performed on the 6th day after transplantation, when the tumor was determined visually and by palpation in all animals. During the experiment, the following parameters determined: tumor growth inhibition (T%), tumor growth kinetics, overall survival (OS) and tumor growth index (TGI). Significant tumor regression observed in the chlonisol group (unpaired t-test; P <0,0001). By the 15th day of the experiment T% was 99%. The administration of chonisol at a dose of 15 mg/kg significantly increased the median OS compared with the control from 15 days to 60,5 days (log-rank test; P <0,0001). Chonisol significantly reduced the risk of death in animals by 84% (HR=0,16; 95% CI 0,06-0,40). Of the 10 animals received chlonisol, in 5 rats complete tumor response documented. These rats survived 90 days without signs of relapse, which can be considered as a complete response. The difference with the control was statistically significant (Fisher's exact test; P=0,0047). The TGI in the test compound group was almost 10 times lower than in the control group. The results obtained demonstrate a high antitumor activity of chlonisol, which confirmed by its pronounced effects on the formed tumor on the 6th day after transplantation. The described quantitative parameters can be used to assess the antitumor activity of not only cytostatics, but also other drugs for cancer management (target therapy, immunotherapy).

Full text avaliable in Russain only

Autors’ contributions

Murazov Ia.G. – conception of the work, data collection and systematization, writing and editing of the manuscript.

Stukov A.N. – data collection and systematization, critical revision of the manuscript.

Zmitrichenko Iu.G. – data collection and systematization.

Tochilnikov G.V. – editing of the manuscript. 

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