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

Abstract

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.

β‐elemene enhances cisplatin sensitivity of non‐small cell lung cancer cells via the miR‐17‐5p/STAT3 axis

“…MiRNAs are implicated in the pathogenesis of multiple human diseases, and some miRNAs have been reported to modulate chemotherapeutic drug sensitivity of cancer cells (Li et al., 2023; Niu et al., 2019; Xu et al., 2019; Yao & Shi, 2023). MiR‐17‐5p modulates chemoresistance of gastric cancer cells by targeting p21 (Wang et al., 2018).…”

“…NSCLC is a deadly human malignancy, and drug development for NSCLC is a hot spot in cancer research (Nguyen et al, 2023;Puri et al, 2023). Notably, some recent published studies have reported that β-elemene represses the malignant biological behaviors of lung cancer cells (Li et al, 2023;Song et al, 2023;Xu et al, 2023;Yao et al, 2014). In this work, we observe that β-elemene decreases the viability of cisplatin-resistant NSCLC cells, which further validates the tumor-suppressive function of β-elemene for NSCLC.…”

“…In this work, we observe that β-elemene decreases the viability of cisplatin-resistant NSCLC cells, which further validates the tumor-suppressive function of β-elemene for NSCLC. MiRNAs are implicated in the pathogenesis of multiple human diseases, and some miRNAs have been reported to modulate chemotherapeutic drug sensitivity of cancer cells (Li et al, 2023;Niu et al, 2019;Xu et al, 2019;Yao & Shi, 2023). MiR-17-5p modulates chemoresistance of gastric cancer cells by targeting p21 .…”

Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer

“…β-elemene is a natural compound that displays antimetastatic efficacy by blocking PKM2 transformation and nuclear translocation [160]. β-elemene can overcome gefitinib resistance by inducing fructose-1,6-bisphosphatase [161]. Licochalcone, a natural compound from Glycyrrhiza uralensis, is a potent HIF-1α inhibitor that can suppress the expression of GLUT1 and PDK1 by inhibiting HIF-1α in HCT116 cells [162].…”