Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023 May

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M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention. Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Citation

Muhammad Tariq, Nadia Hussain, Kanwal Rehman, Muhammad Sajid Hamid Akash, Amal H I Al Haddad, Amira S A Said, Adel Al Fatease, Ali Alamri, Awaji Y Safhi, Fahad Y Sabei, Ahmed Abdullah Al Awadh, Musaddique Hussain. Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023 May;161:114527