Objective: Estrogen may have a certain role in promoting lung cancer caused by tobacco. Our understanding of the carcinogenic effects and mechanisms of carcinogen mixture estrogen is limited and mostly relies on the findings from studying individual factors.
Methods: To test this hypothesis, an in-vitro study was used to investigate the effects of 17 β-estradiol (E2) on benzo[a]pyrene (Bap)-induced lung cancer cell A549 proliferation.
Results: We first found that E2 was increased in serum samples from lung adenocarcinoma cancer (LUAD) patients, even to a small extent. We found that Bap could enhance colony formation ability, up-regulate proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (Bcl-2) expression, induce cell proliferation and inhibit apoptosis in A549 cells. E2 promoted these effects of Bap. Moreover, E2 and Bap co-exposure promoted lung cancer cell proliferation by activating the aryl hydrocarbon receptor (AHR)/protein kinase B (AKT)/extracellular regulated protein kinases (ERK1/2) signaling pathway. Inhibition of the AKT and ERK1/2 signaling pathways suppressed E2 and Bap co-exposure's effect on A549 cells proliferation and apoptosis.
Conclusions: Collectively, we conclude that E2 could promote the proliferative and antiapoptotic effects of Bap on A549 cells, and activation of the AHR/AKT/ERK1/2 pathway may be involved in this process.
Keywords: benzo[a]pyrene; estradiol; lung cancer; proliferation.
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