Effects of bisphenol A on the proliferation, migration, and tumor growth of colon cancer cells: In vitro and in vivo evaluation with mechanistic insights related to ERK and 5-HT3

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical related to the carcinogenesis of estrogen responsive organs. Although human exposure to BPA mainly occurs via the oral route, its association with colon cancer has not been fully elucidated. We investigated the effects of BPA on the proliferation, migration, and tumor growth of colon cancer cells. BPA significantly promoted the proliferation of HT-29 human colon adenocarcinoma cells in a time-and dose-dependent manner. BPA also increased HT-29 cells migration. BPA increased the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibition of the ERK pathway attenuated BPA-induced proliferation and migration. In addition, BPA reduced E-cadherin expression, a key factor impeding epithelial-to-mesenchymal transition, and increased 5-HT3 receptors expression, a major mitogenic factor. In xenograft models, tumor volume of the BPA-treated nude mice was 4.6 times that of the saline-treated group. Our findings provide primary evidence regarding the link between BPA and human colon cancer by demonstrating that BPA promotes the proliferation, migration, and tumor growth of colon cancer cells in both in vitro and in vivo models. In addition, we provided the mechanism of action of BPA, involved in the activation of the ERK pathway, the decrease in E-cadherin, and the increase in 5-HT3 receptors.

Automated summary

BPA promotes proliferation and migration of colon cancer cells, decreases E-cadherin expression, and increases 5-HT3 receptor expression. In nude mouse xenograft models, tumor volume was significantly higher in the BPA-treated group.