Downregulation of HOTAIR Expression Mediated Anti-Metastatic Effect of Artesunate on Cervical Cancer by Inhibiting COX-2 Expression.

Lixin Zhang,Lixin Zhang,Zhengyun Luan,Xiaokang Li,Xiaokang Li,Min Sha,Min Sha,Lihua Ye,Lihua Ye,Donglan Yuan,Hua Qian,Hua Qian,Donglan Yuan,Mei Lin,Junxing Huang,Junxing Huang,Zhengyun Luan,Zhiqian Zhang

doi:10.1371/journal.pone.0164838

Lixin Zhang, Lixin Zhang + Show 16 more

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https://doi.org/10.1371/journal.pone.0164838

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Journal: PloS one	Publication Date: Oct 13, 2016
Citations: 30	License type: CC BY 4.0

Affiliation: Taizhou People's Hospital, Nantong University

Abstract

Artesunate (ART) has anti-cancer activities for a variety of solid tumors. The aim of this study was to investigate the anti-metastatic effect of ART on cervical cancer cells. In vivo anti-metastatic effect of ART was investigated in mice with the lung metastasis model by the subcutaneous injection of ART. The interaction of HOTAIR and COX-2 was measured by RNA immunoprecipitation and RNA pull-down assay. The effect of ART on metastasis of CaSki and Hela cells was evaluated by invasion and migration assay. We found that ART inhibited cervical cancer metastasis and HOTAIR expression. HOTAIR overexpression partially abolished the anti-metastatic effect of ART on cervical cancer cells. In addition, HOTAIR can interact with COX-2 to positively regulate COX-2 expression and catalytic activity. Finally, overexpression of COX-2 reversed the effect of HOTAIR knockdown on Hela cell migration and invasion. Taken together, our data revealed that ART may elicit anti-metastatic effect against cervical cancer by inhibition of HOTAIR expression, which resulted in the decrease of COX-2 expression.

Highlights

Cervical cancer is a leading cause of cancer-related death among females worldwide, in developing countries [1]
We have found that HOTAIR expression was significantly inhibited in cervical cancer cells induced by ART
Our results showed that ART significantly decreased HOTAIR expression in cervical cancer cells (Fig 2B)

Summary

Introduction

Cervical cancer is a leading cause of cancer-related death among females worldwide, in developing countries [1]. The 5-year survival rate is about 90% if patients were treated in the early stages. Patient outcome is poor when the cancer has metastasized [2]. The traditional strategies for the treatment including surgery, radiotherapy and chemotherapy are not effective to metastatic patients and have severe side effects [3]. There is a renewed interest in the use of natural sources to treat cervical cancer.

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