FBP1 induced by β‐elemene enhances the sensitivity of gefitinib in lung cancer

BACKGROUND: β‐elemene is known to play a critical role in tumorigenesis as well as tyrosine kinase inhibitor (TKI) resistance in lung cancer. However, the biological function and molecular mechanism remain largely unknown. METHODS: In this study, the common genes involved in gefitinib resistance and β‐elemene were identified using bioinformatic analysis. The expression of FBP1 was examined by qRT–PCR and Western blot analysis. Cell proliferation, flow cytometry, clone formation and IC50 assays were performed to assess the effects of β‐elemene and FBP1. Western blot analysis was used to evaluate apoptosis‐related gene expression. Finally, in vivo experiments were conducted to assess the crucial role of FBP1 in gefitinib‐resistant HCC827/GR cells in nude mice. RESULTS: Screening analysis demonstrated that fructose‐1,6‐bisphosphatase (FBP1) was induced by β‐elemene and downregulated in gefitinib‐resistant lung cells. Functionally, overexpression of FBP1 inhibited proliferation and gefitinib resistance and promoted apoptosis of PC9/GR and HCC827/GR cells in vitro. Mechanistically, FBP1 impeded the nuclear translocation of p‐STAT3. The FBP1/STAT3 axis was required for FBP1‐mediated apoptosis‐related gene expression. In vivo experiments further confirmed the enhanced effects of FBP1 on lung cancer cell sensitivity to gefitinib. CONCLUSION: Our research indicated that β‐elemene suppressed proliferation and enhanced sensitivity to gefitinib by inducing apoptosis through the FBP1/STAT3 axis in gefitinib‐resistant lung cancer cells.