Bisphenol A induces expression of LRP and MDR process in lung cancer cells in vitro

Objective To declare whether BPA (Bisphenol A) induces the expression of LRP (lung resistance protein) and MDR (multi-drug resistance) process in vitro. Methods Series concentration gradient of BPA was used in dose-effect experiments inducing LRP expression. Then, ELISA assay was used to identify the effect of BPA on LRP and the EC₅₀ value (50% effective concentration) was calculated. The inhibition rate of anti-tumor drugs on A549 or A549/ADR was calculated by A_490nm from MTT assays and IC₅₀ values (50% inhibitory concentration) were calculated. Protein level of LRP induced by BPA with EC₅₀ concentration and the expression of LRP in A549/ADR were detected by western blot analysis. The small interfering RNA (siRNA) of LRP was transfected into A549/ADR cells to downregulate protein level of LRP, and its effect on MDR was investigated. Results Results from ELISA showed that BPA induced the expression of LRP in a dose-dependent manner (EC₅₀=0.55±0.12 μmol/L, R²=0.96, P=0.001 1), and BPA (EC₅₀ concentration) could downregulate the effects of Paclitaxel, Gemcitabine and Gefitinib to A549 with significant increase of IC₅₀ value(0.08±0.01) μmol/L vs (0.67±0.11) μmol/L, P< 0.05; (0.45±0.05) μmol/L vs (2.75±0.33) μmol/L, P< 0.05; (1.36±0.22) μmol/L vs (5.82±0.41) μmol/L, P< 0.05 and drug resistance of 7.12, 6.11, 4.28 times. In addition, Western blot analysis showed that high level of LRP was detected in A549/ADR cells compared with A549 cells. Transfection of LRP siRNA downregulated LRP expression and enhanced the sensitivity of A549/ADR cells to Paclitaxel(0.59±0.07) μmol/L vs (0.15±0.06) μmol/L, P< 0.05, Gemcitabine(3.95±0.66) μmol/L vs (0.86±0.14) μmol/L, P< 0.05 or Gefitinib(8.72±0.71) μmol/L vs (1.99±0.54) μmol/L, P< 0.05. Conclusion BPA can induce the expression of LRP and will participate in the MDR process in human lung cancer cells.