Dual phase modeling of Chrysotile carcinogenesis from 3D cell transformation to orthotopic tumors.

Abstract

Chrysotile asbestos, a well-established carcinogen, is known to induce various malignant cancers, contributing to an estimated annual death toll of 107,000 individuals due to asbestos-related diseases. While cell and animal models play a crucial role in elucidating the carcinogenic mechanisms of asbestos, existing models are plagued by prolonged experimental durations. In this investigation, we established a novel NIH/3T3 cell model of asbestos-induced malignant transformation using 3D culture techniques, followed by the development of a corresponding mouse model via orthotopic transplantation. Subsequent administration of the HIF-1α inhibitor PX-478 to both models allowed for the assessment of model reliability through the observation of malignant phenotypes and associated protein alterations.