Propofol suppresses LPS-induced nuclear accumulation of HIF-1α and tumor aggressiveness in non-small cell lung cancer

Yang,Nengli; Liang,Yafeng; Yang,Pei; Ji,Fuhai

doi:10.3892/or.2017.5514

Propofol suppresses LPS-induced nuclear accumulation of HIF-1α and tumor aggressiveness in non-small cell lung cancer

Authors:
- Nengli Yang
- Yafeng Liang
- Pei Yang
- Fuhai Ji
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: March 17, 2017 https://doi.org/10.3892/or.2017.5514
Pages: 2611-2619
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor hypoxia has been recognized as a characteristic of the tumor microenvironment and promotes metastasis in a variety of types of cancer. However, in lung cancer, the role of hypoxia-inducible factor 1α (HIF-1α) in modulating the cellular response to the inflammation-related microenvironment remains unclear. In the present study, enhanced expression of HIF-1α accompanied by an increased ROS level was observed in lipopolysaccharide (LPS)-stimulated non-small cell lung cancer (NSCLC) cells. In addition, propofol, a general anesthetic, was found to significantly reduce the LPS-induced upregulation of HIF-1α and ROS in a dose-dependent manner. Further study showed that propofol may antagonize the role of LPS in activating HIF-1α through attenuating the protein stability and nuclear localization of HIF-1α. Moreover, knockdown of HIF-1α attenuated expression of mesenchymal marker, vimentin, but promoted the expression of epidermal marker, E-cadherin, in the LPS-treated NSCLC cells. Notably, LPS-induced epithelial-to-mesenchymal transition (EMT) was notably suppressed by propofol treatment. Consistently, a wound healing assay revealed that propofol abrogated LPS-stimulated migration of NSCLC cells while overexpression of HIF-1α reversed the effects of propofol. Similarly, we investigated the influence of propofol on the invasive capability of NSCLC cells. Western blot and RT-PCR analyses indicated that both knockdown of HIF-1α and treatment of propofol attenuated the LPS-activated expression of MMP2 and MMP9 which are necessary for tumor invasion. However, results from the Transwell assay confirmed that propofol also suppressed cell invasion by decreasing HIF-1α expression in the LPS-treated NSCLC cells. Analysis of clinical specimens demonstrated abnormal expression of HIF-1α in NSCLC tissues and a poor prognosis in patients with elevated HIF-1α expression. Thus, the present study suggests a potential strategy for NSCLC by targeting HIF-1α.

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