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

Author(s):

Na Peng, Meijun Lu, Mafei Kang*, Xiuli Liu, Bihui Li and Cuimei Dong   Pages 1996 - 2003 ( 8 )

Abstract:

<p>Background: Interleukin-11 (IL-11) could promote invasion and metastasis of cancer cells, however, its mechanism is unclear. </P><P> Objective: This study aimed to investigate the effects of recombinant human IL-11 (rhIL-11) on lung cancer cell metastasis and growth. </P><P> 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 1&#945; (HIF1&#945;), 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). </P><P> Results: Sizes of subcutaneous tumors increased following measurement time. rhIL-11 treatment significantly enhanced HIF1&#945; 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). </P><P> Conclusion: rhIL-11 transplantation promoted growth and Epithelial-Mesenchymal Transition (EMT) of A549 cells, which might be associated with STAT3/HIF-1&#945;/EMT signaling pathway activation.</p>

Keywords:

Interleukin-11, epithelial-mesenchymal transition, hypoxia-inducible factor 1&#945;, lung cancer, signaling pathway, STAT3.

Affiliation:

Department of Medical Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, Department of Medical Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, Department of Medical Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, Department of Medical Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, Department of Medical Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, Department of Medical Oncology, The Affiliated Hospital of Guilin Medical University, Guilin

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