Antitumor efficacy of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in lung cancer xenografts
| Autor: | Dmitry Aleksandrovich Shvyrev, E.A. Lukbanova, Ekaterina V. Zaikina, Evgeniy A. Gusakov, D. V. Khodakova, Yuriy A. Sayapin, Yuriy N. Lazutin, Irina A. Khomutenko, M. V. Mindar, Alexey N. Shevchenko, Anna S. Goncharova, Elena V. Filatova, A. V. Volkova |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 39:e15008-e15008 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | e15008 Background: Lung cancer is the most common cancer worldwide. The efficacy of chemotherapy for this tumor does not exceed 40%. Moreover, all cytotoxic agents cause many side effects. The search for new substances with an antitumor effect seems to be relevant. Tropolone alkaloids, which are seven-membered non-benzenoid aromatic compounds, are promising inhibitors of tumor growth. The purpose of the study was to evaluate the antitumor efficacy of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in subcutaneous xenografts of lung cancer A549 cells in immunodeficient Balb/c Nude mice. Methods: The study was performed on a PDX model of lung cancer created by subcutaneous injection of A549 cell suspension, 5x106 cells in 0.2 ml of a solution of serum-free nutrient medium 199 and Matrigel (1:1). Animals were equally divided into 5 groups (each n = 5). Experimental groups 1, 2, 3 and 4 received 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone at doses of 0.0055, 0.055, 0.55 and 2.75 mg/g, respectively; the control group received 1% starch gel. The dynamics of the growth of a subcutaneous xenograft was evaluated by measuring tumor nodes. The volumes of tumor nodes were calculated using the Shrek’s formula for the ellipsoid: V = a×b×c×p/6, where V is the tumor volume (mm3), and a, b, c are the maximum dimensions of the ellipsoid in three planes (mm). The data were statistically analyzed using the Exel and Medstatistic progams. Results: The dynamics of subcutaneous xenograft growth in groups 1, 2, 3 and 4 significantly differed from the control group (p = 0.023). The average tumor volumes on the 39th day after the implantation in the control group and in experimental groups 1, 2, 3 and 4 were 1159.2, 895.3, 565.8, 80.7 and 76.7 mm3, respectively. The inhibition of tumor growth (ITG) was in direct proportion to the dose of the administered substance. Lower ITG(%) (32.4, 23.2 and 10.3% in experimental groups 2, 3 and 4, respectively) was associated with lower concentrations of О154 (0.55 mg/g, 0.055 mg/g and 0.0055 mg/g, respectively). Conclusions: The study demonstrated statistically significant differences in xenograft volume indices in all experimental groups compared to the control group. |
| Databáze: | OpenAIRE |
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