Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma
Joint Authors
Zhou, Yinghong
Dong, Xiaofeng
Xiu, Peng
Wang, Xin
Yang, Jianrong
Li, Lei
Li, Zhongchao
Sun, Pengfei
Shi, Xuetao
Zhong, Jingtao
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-03-24
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of hypoxia-inducible factor (HIF).
Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, induces cell death in various malignancies.
However, the underlying mechanism remains to be elucidated in HCC, especially under hypoxic conditions.
The alteration of COX-2 and HIF-1α oncogenicity was evaluated in HCC specimens by tissue microarray.
Cell viability, angiogenesis assays, and xenografted nude mice were used to evaluate the effects of meloxicam, along with flow cytometry to detect the cell cycle, apoptosis, and mitochondrial membrane potential (ΔΨm) of HCC.
qRT-PCR, Western blotting, immunofluorescence, immunohistochemistry, luciferase assay, and RNAi were carried out to determine the HIF-1α signaling affected by meloxicam.
In this study, we showed that meloxicam exerts antiproliferative and antiangiogenesis efficacy in vitro and in vivo and causes disruption of mitochondrial membrane potential (ΔΨm), thus leading to caspase-dependent apoptosis under hypoxic environments.
Exposure to meloxicam significantly reduced HIF-1α transcriptional activation and expression through sequestering it in the cytoplasm and accelerating degradation via increasing the von Hippel-Lindau tumor suppressor protein (pVHL) in HCC.
These data demonstrated that inhibition of HIF-1α by meloxicam could suppress angiogenesis and enhance apoptosis of HCC cells.
This discovery highlights that COX-2 specific inhibitors may be a promising therapy in the treatment of HCC.
American Psychological Association (APA)
Zhou, Yinghong& Dong, Xiaofeng& Xiu, Peng& Wang, Xin& Yang, Jianrong& Li, Lei…[et al.]. 2020. Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1205277
Modern Language Association (MLA)
Zhou, Yinghong…[et al.]. Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1205277
American Medical Association (AMA)
Zhou, Yinghong& Dong, Xiaofeng& Xiu, Peng& Wang, Xin& Yang, Jianrong& Li, Lei…[et al.]. Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1205277
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205277