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, Cuimei Dong

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 21 , Issue 15 , 2021


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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, epithelial-mesenchymal transition, hypoxia-inducible factor 1α, lung cancer, signaling pathway, STAT3.

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Article Details

VOLUME: 21
ISSUE: 15
Year: 2021
Published on: 06 December, 2020
Page: [1996 - 2003]
Pages: 8
DOI: 10.2174/1871520621666201207091248
Price: $65

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