STAT3 Pathways Contribute to β-HCH Interference with Anticancer Tyrosine Kinase Inhibitors

STAT3 通路参与 β-HCH 对抗癌酪氨酸激酶抑制剂的干扰

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作者:Sara Fiorini, Elisabetta Rubini, Monia Perugini, Fabio Altieri, Silvia Chichiarelli, Giorgia Meschiari, Giulia Arrighetti, John Vijgen, Pier Giorgio Natali, Marco Minacori, Margherita Eufemi

Abstract

Organochlorine pesticides (OCPs) are a class of environmentally persistent and bioaccumulative pollutants. Among these, β-hexachlorocyclohexane (β-HCH) is a byproduct of lindane synthesis, one of the most worldwide widespread pesticides. β-HCH cellular mechanisms inducing chemical carcinogenesis correspond to many of those inducing chemoresistance, in particular, by the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathways. For this purpose, four cell lines, representative of breast, lung, prostate, and hepatocellular cancers, were treated with β-HCH, specific tyrosine kinase inhibitors (TKIs), and a STAT3 inhibitor. All cell samples were analyzed by a viability assay, immunoblotting analysis, a wound-healing assay, and a colony formation assay. The results show that β-HCH reduces the efficacy of TKIs. The STAT3 protein, in this context, plays a central role. In fact, by inhibiting its activity, the efficacy of the anticancer drug is restored. Furthermore, this manuscript aimed to draw the attention of the scientific and socio-healthcare community to the issue of prolonged exposure to contaminants and their impact on drug efficacy.

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