Oncotarget

Research Papers:

Combined treatment with artesunate and bromocriptine has synergistic anticancer effects in pituitary adenoma cell lines

Xin Wang, Qiu Du, Zhigang Mao, Xiang Fan, Bin Hu, Zhen Wang, Zhiyong Chen, Xiaobing Jiang, Zongming Wang, Ni Lei, Haijun Wang _ and Yonghong Zhu

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Oncotarget. 2017; 8:45874-45887. https://doi.org/10.18632/oncotarget.17437

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Abstract

Xin Wang1,2,*, Qiu Du1,*, Zhigang Mao2, Xiang Fan3, Bin Hu2, Zhen Wang1, Zhiyong Chen2, Xiaobing Jiang2, Zongming Wang2, Ni Lei1, Haijun Wang2 and Yonghong Zhu1

1Department of Histology and Embryology, Medical School of Sun Yat-Sen University, Guangzhou, China

2Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

3Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China

*These authors have contributed equally to this work

Correspondence to:

Haijun Wang, email: [email protected]

Yonghong Zhu, email: [email protected]

Keywords: pituitary adenoma, synergistic treatments, miR-200c, Pten

Received: April 13, 2016     Accepted: April 11, 2017     Published: April 26, 2017

ABSTRACT

Prolactinomas are the most prevalent functional pituitary adenomas. The preferred treatments for prolactinomas are dopamine agonists (DAs) such as bromocriptine (BRC), but DAs still have the challenges of tumor recurrence and drug resistance. This study demonstrates that the synergy of function and mechanism between artesunate (ART) and BRC inhibits prolactinoma cell growth in vitro. We found that low-dose ART combined with BRC synergistically inhibited the growth of GH3 and MMQ cell lines, caused cell death, attenuated cell migration and invasion, and suppressed the expression of extracellular prolactin. The induction of apoptosis after co-treatment was confirmed by immunofluorescent staining, assessment of caspase-3 protein expression, and flow cytometry. Expression of miR-200c, a carcinogenic factor in pituitary adenoma, was reduced following co-treatment with ART and BRC. This was accompanied by increased expression of the antitumor factor Pten. Transfection experiments with miR-200c analogs and inhibitors confirmed that miR-200c expression was inversely associated with Pten expression. We suggest that ART and BRC used in combination exert synergistic apoptotic and antitumor effects by suppressing miR-200c and stimulating Pten expression.


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