Recombinant Human IL-11 Promotes Lung Adenocarcinoma A549 Cell Growth and EMT through Activating STAT3/HIF-1α/EMT Signaling Pathway

Anticancer Agents Med Chem. 2021;21(15):1996-2003. doi: 10.2174/1871520621666201207091248.

Abstract

Background: Interleukin-11 (IL-11) could promote invasion and metastasis of cancer cells, however, its mechanism is unclear.

Objective: This study aimed to investigate the effects of recombinant human IL-11 (rhIL-11) on lung cancer cell metastasis and growth.

Methods: Human lung cancer cell, A549, was cultured and subcutaneously injected into mice to establish Xenograft tumor models. Tumor models were divided into control, rhIL-11 transplantation (250 μg/kg/day), and rhIL-11 transplantation (500 μg/kg/day) group. Tumor volumes were recorded and measured 6 times. Hypoxia- Inducible Factor 1α (HIF1α), snail, slug, Signal Transducers/Activators of Transcription-3 (STAT3), E-cadherin, twist, and vimentin levels were evaluated using western blot and Real-Time PCR (RT-PCR).

Results: Sizes of subcutaneous tumors increased following measurement time. rhIL-11 treatment significantly enhanced HIF1α and STAT3 expression in rhIL-11 treatment groups compared to the control group (p<0.05). However, no remarkable differences were discovered between rhIL-11 (250 μg/kg/day) and rhIL-11 (500 μg/kg/day) group (p>0.05). rhIL-11 treatments significantly increased twist, and slug expressions compared to control group (p<0.05), especially for rhIL-11 (500 μg/kg/day) treatment, which triggered significantly higher effects on twist and slug expressions compared to those in the control group (p<0.05). Vimentin and snail mRNA levels were significantly up-regulated and E-cadherin level was significantly down-regulated in rhIL-11 treatment groups compared to the control group (p<0.05). Meanwhile, rhIL-11 at a dosage of 500 μg/kg/day triggered remarkably higher effects on vimentin, snail, and E-cadherin expressions compared to those in rhIL-11 (250 μg/kg/day) group (p<0.05).

Conclusion: rhIL-11 transplantation promoted growth and Epithelial-Mesenchymal Transition (EMT) of A549 cells, which might be associated with STAT3/HIF-1α/EMT signaling pathway activation.

Keywords: Interleukin-11; STAT3.; epithelial-mesenchymal transition; hypoxia-inducible factor 1α; lung cancer; signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / therapy*
  • Animals
  • Antineoplastic Agents / metabolism*
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Interleukin-11 / metabolism*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Mice
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • IL11 protein, human
  • Interleukin-11
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human