Immunohistochemistry for assessing toxicity and mechanism of action of anticancer drugs during preclinical trials. From theory to practice

Aim. To identify the most suitable pathogenetic mechanisms for in-depth study of the antitumor and antimetastatic effects of tested hybrid organotin compounds using the immunohistochemical approach.Materials and Methods. Here, we tested bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (lab...

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Main Authors: M. A. Dodokhova, M. A. Akimenko, O. V. Voronova, M. S. Alkhusein-Kulyaginova, N. A. Kornienko, M. V. Gulyan, D. N. Gyulmamedov, M.-M. Kh. Alasheva, E. Sh. Kazimagomedova, D. B. Shpakovsky, E. R. Milaeva, I. M. Kotieva
Format: Article
Language:Russian
Published: Kemerovo State Medical University 2024-09-01
Series:Фундаментальная и клиническая медицина
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Online Access:https://fcm.kemsmu.ru/jour/article/view/903
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Summary:Aim. To identify the most suitable pathogenetic mechanisms for in-depth study of the antitumor and antimetastatic effects of tested hybrid organotin compounds using the immunohistochemical approach.Materials and Methods. Here, we tested bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (laboratory code Me-3), belonging to the class of hybrid organotin compounds, on 30 female C57Bl/6 mice using a universal model of transplantable tumors with spontaneous metastasis (B16 melanoma). 48 hours after tumor cell transplantation, we intraperitoneally administered Me-3 once daily to female C57Bl/6 mice for 10 days at a total dose (TD) of 375 mg/kg. For histological analysis, we used the primary tumor node of B16 melanoma. Immunophenotyping of B16 melanoma tissue samples was carried out using the polyclonal antibodies to transforming growth factor beta 1 (TGFβ-1), vascular endothelial growth factor A (VEGFA), Bcl2-associated X Protein (Bcl-2), cluster of differentiation 34 (CD34).Results. After the exposure to Me-3, we found a reduced immunohistochemical signal to TGF-β1 and Bcl-2 3 in the tumor tissue. Low doses of Me-3 have also impacted angiogenesis.Conclusion. Me-3 has a pro-apoptotic and anti-angiogenetic effects on B16 melanoma cells in C57Bl/6 mice.
ISSN:2500-0764
2542-0941