Abstract:
Background Bisphenol A (BPA) is a common environmental endocrine disruptor with a similar chemical structure to estrogen. In recent years, the relationship between BPA and tumors has attracted widespread attention. The effects of BPA on the development of thyroid cancer, with the highest incidence rate among endocrine system cancers, are worth exploring further.
Objective This experiment investigates the effects and mechanisms of BPA on the proliferation of human papillary thyroid carcinoma cells.
Methods Human papillary thyroid carcinoma KTC-1 cells were cultured in vitro and passaged before the cells were randomly divided into two groups:control group and BPA experiment group (subgrouping by BPA concentrations at 5×10-3, 5×10-4, 5×10-5, 5×10-6, 5×10-7, 5×10-8, and 5×10-9 mol·L-1). After 24 h, 48 h, and 72 h exposure, CCK-8 experiment was used to detect the cell proliferation rate, inverted microscope was used to observe the morphological changes of cells, flow cytometry was used to analyze cell cycle, and Western blotting was used to detect the expression levels of Cyclin D1 and P21.
Results BPA at 5×10-3 mol·L-1 induced massive cell death as the cells were floated in the medium, residual adherent cells were vacuolated, cell connection disappeared, and the morphological changes were more obvious with extended exposure time. The cells treated with BPA at 5×10-7 and 5×10-9 mol·L-1 were spindle-shaped, and significant cell division was observed. Compared with the control group, BPA at 5×10-3, 5×10-4, and 5×10-5 mol·L-1 significantly reduced the cell proliferation rate at different time points (24 h, 48 h, and 72 h) (P < 0.05); BPA at 5×10-7, 5×10-8, and 5×10-9 mol·L-1 increased the cell proliferation rate at 48 h (P < 0.001); BPA at 5×10-6 mol·L-1 decreased the cell proliferation rate at 24 h, and increased the rate at 48 h and 72 h (P < 0.001). The results of flow cytometry showed that the cell proliferation index (PI) of the subgroups except the 5×10-5 mol·L-1 BPA subgroup presented a rising tendency compared with the control group, but there was no significant difference. The proportion of cells in S phase of the 5×10-6 mol·L-1 BPA subgroup was significantly higher than that of the control group (P < 0.05). Compared with the control group, the expression level of Cyclin D1 protein decreased and the expression level of P21 protein increased in the 5×10-5 mol·L-1 BPA subgroup; in contrast, the expression level of Cyclin D1 protein increased and the expression level of P21 protein decreased in the 5×10-8 and 5×10-9 mol·L-1 BPA subgroups (P < 0.05).
Conclusion BPA has dual effects on the proliferation of KTC-1 cells. High-dose BPA has a toxic effect on KTC-1 cells and leads to cell death; low-dose BPA promotes the proliferation of KTC-1 cells. Different concentrations of BPA can either promote or inhibit the proliferation of KTC-1 cells by regulating the expression of Cyclin D1 and P21.
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