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

Chem Biol Drug Des. 2024 Jan;103(1):e14395. doi: 10.1111/cbdd.14395. Epub 2023 Nov 16.

Abstract

In China, β-elemene, a sesquiterpene compound derived from Curcuma wenyujin, is clinically used to treat many human malignancies, including non-small cell lung cancer (NSCLC). Nonetheless, the role of β-elemene in regulating cisplatin sensitivity of NSCLC cells and the related mechanisms are not clear. This study was conducted to investigate the role of β-elemene in sensitizing NSCLC cells to cisplatin. In this work, cisplatin-resistant NSCLC cell lines were constructed. CCK-8, colony formation, and flow cytometry assays were executed to examine cell viability, growth, and apoptosis. MiR-17-5p and STAT3 expression levels in cells were detected by qRT-PCR. Western blot was executed to determine the expression levels of STAT3 and apoptosis-related proteins (Bax and Bcl-2) in the cells. Dual-luciferase reporter gene experiments were performed to verify the targeting relationship between miR-17-5p and STAT3. Herein, we report that, β-elemene inhibits the viability, and induces the apoptosis of cisplatin-resistant NSCLC cells. Additionally, β-elemene induces the upregulation miR-17-5p and downregulation of STAT3. STAT3 is validated to be a target of miR-17-5p in NSCLC cells. Additionally, the role of β-elemene to repress the viability of cisplatin-resistant NSCLC cells is partially counteracted by miR-17-5p inhibitor or STAT3 overexpression. In summary, our study suggests that β-elemene enhances cisplatin sensitivity of NSCLC cells by modulating miR-17-5p/STAT3 axis, and it may be a choice for the complementary treatment of NSCLC patients.

Keywords: NSCLC; STAT3; cisplatin; miR-17-5p; β-elemene.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / metabolism
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Sesquiterpenes* / pharmacology

Substances

  • Cisplatin
  • beta-elemene
  • MicroRNAs
  • Sesquiterpenes
  • STAT3 protein, human
  • STAT3 Transcription Factor
  • MIRN17 microRNA, human