Kovalenko L P, Korzhova K V, Zainullina L F, Nikitin S V, Ivanova E A, Zhurikov R V
Zakusov Institute of Pharmacology, Moscow, Russia.
Biomed Khim. 2021 Mar;67(2):158-161. doi: 10.18097/PBMC20216702158.
The effects of intraperitoneal administration of SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) in a dose of 25 mg/kg (the total dose of 350 mg/kg) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5- hydroxypyrimidine) in a dose of 10 mg/kg (the total dose of 140 mg/kg) on tumor growth and concentration of cytokines in the blood serum were studied in female CBA mice. Substances were administrated from the 2nd to 15th days of tumor development. Tumor growth inhibition (TGI) and serum cytokine level were studied on the 7th day after the end of compounds administration (21st day of tumor growth). In intact control group (n=10) median tumor mass was 1255 mg. TGI in the group of animals treated with SNK-411 was 47%; in the group of mice treated with SNK-578 TGI was 87%, tumor mass demonstrated 7.4-fold reduction. Serum concentrations of cytokines (IL-6, IL-10, IL-17A and IFN-γ) in tumor-bearing group of mice were higher versus the intact control group by 229%, 40%, 60% and 81%, respectively. Highly active SNK-578 decreased concentrations of prooncogenic IL-10, IL-17A and proinflammatory IL-6, by 61%, 70% and 29% as compared to tumor-bearing control group. SNK-411 decreased concentrations of prooncogenic IL-10 and IL-17A by 48% and 60%, respectively, and did not affect concentration of IL-6. Taking into consideration that IL-6 participates in autoimmune reactions, we can assume that the immune control is one of the crucial mechanisms of antitumor effect of SNK-578. All results are statistically significant.
在雌性CBA小鼠中，研究了腹腔注射剂量为25mg/kg（总剂量350mg/kg）的SNK - 411（2 - 异丁基 - 4,6 - 二甲基 - 5 - 羟基嘧啶）和剂量为10mg/kg（总剂量140mg/kg）的SNK - 578（2 - 异丁基 - 4,6 - 二甲基 - 5 - 羟基嘧啶盐酸盐）对肿瘤生长和血清中细胞因子浓度的影响。从肿瘤发生的第2天至第15天给予这些物质。在化合物给药结束后第7天（肿瘤生长第21天）研究肿瘤生长抑制（TGI）和血清细胞因子水平。在完整对照组（n = 10）中，肿瘤中位数质量为1255mg。用SNK - 411治疗的动物组中TGI为47%；用SNK - 578治疗的小鼠组中TGI为87%，肿瘤质量显示降低了7.4倍。荷瘤小鼠组血清细胞因子（IL - 6、IL - 10、IL - 17A和IFN - γ）浓度分别比完整对照组高229%、40%、60%和81%。高活性的SNK - 578与荷瘤对照组相比，使促癌性IL - 10、IL - 17A和促炎性IL - 6的浓度分别降低了61%、70%和29%。SNK - 411使促癌性IL - 10和IL - 17A的浓度分别降低了48%和60%，并且不影响IL - 6的浓度。考虑到IL - 6参与自身免疫反应，我们可以假设免疫控制是SNK - 578抗肿瘤作用的关键机制之一。所有结果均具有统计学意义。
