Effect of Poly(methacrylic acid) on the Cytokine Level in an In Vivo Tumor Model

Abstract

Cancer is a leading cause of mortality globally. Despite remarkable improvements in cancer-treatment approaches, disease recurrence and progression remain major obstacles to therapy. While chemotherapy is still a first-line treatment for a variety of cancers, the focus has shifted to the development and application of new approaches to therapy. Nevertheless, the relationship between immune response, neoplastic diseases and treatment efficiency is not fully understood. Therefore, the aim of the study was to investigate the immunopharmacological effects of methacrylic acid homopolymer in an in vivo tumor model. Materials and methods: Monomeric methacrylic acid was used to synthesize polymers. Methacrylic acid was polymerized in dioxane in the presence of 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid. To study the molecular weight characteristics of PMAA by GPC, carboxyl groups were preliminarily methylated with diazomethane. An experimental cancer model was obtained by grafting RMK1 breast cancer cells. The serum levels of IL-6, IL-10, IL-17, transforming growth factor β1 (TGF-β1), and tumor necrosis factor α (TNF-α) were measured by ELISA. Results: The effect of PMAA on the serum concentrations of several cytokines was studied upon its single administration to laboratory animals in early neoplastic process. The IL-6, IL-17 and TGF-β1 concentrations were found to change significantly and reach the level observed in intact rats. The IL-10 concentration tended to normalize. Conclusion: The positive results obtained are the basis for further studies on the effect of methacrylic-acid polymers with different molecular-weight characteristics on the neoplastic process.

Specifics of Pharmacokinetics and Biodistribution of 5-Fluorouracil Polymeric Complex

“…The concentration of IL-10 tended to normalize. The data obtained indicate that PMAA has a positive effect on the tumor process at an early stage of its growth [40].…”

“…Polymeric particles are of interest in this direction, given the fact that they are used as carriers for antitumor agents. In the course of this study, an assessment of a polymeric complex based on low-molecular-weight PMAA was carried out, for which an immunopharmacological effect is noted [30,40,[47][48][49].…”

Astragaloside IV, as a potential anticancer agent

“…A large number of inflammatory cells, especially macrophages, exist before tumor invasion. Tumor-associated macrophages regulate inflammation and adaptive immunity by producing TGF-β1 and cytokines (TNF-α and IL-6) and promote angiogenesis and cell proliferation (Zhukova et al, 2022). The expression of TNF-α in the tumor microenvironment is a common feature of numerous malignant tumors, and it can promote the metastasis and invasion of various kinds of tumor cells (Wu and Zhou, 2010).…”

“…Inflammatory cytokine IL-6 is another important inflammatory cytokine, and it is closely related to inflammation and tumor. IL-6 can activate the TGF-β1 pathway to promote cancer cell invasion (Zhukova et al, 2022). Macrophages in the tumor microenvironment regulate inflammation and adaptive immunity by producing growth factors (e.g., TGF-β1) and cytokines (e.g., TNF-α and IL-6), thereby enhancing angiogenesis (Hinshaw and Shevde, 2019).…”