Format

Send to

Choose Destination
Eur J Pharmacol. 2018 Apr 5;824:11-16. doi: 10.1016/j.ejphar.2018.01.040. Epub 2018 Jan 31.

MEHP promotes the proliferation of cervical cancer via GPER mediated activation of Akt.

Author information

1
Yinzhou People's Hospital, Baizhang East Road No.251, Yinzhou District, Ningbo City, Zhejiang Province 315040, PR China.
2
Yinzhou People's Hospital, Baizhang East Road No.251, Yinzhou District, Ningbo City, Zhejiang Province 315040, PR China. Electronic address: drxueheli@163.com.

Abstract

Cervical cancer is the fourth leading cause of cancer death in females worldwide and the second leading cause of mortality among women. Estrogenic signals can regulate the progression of cervical cancer, however, little is known about the mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, on the development of cervical cancers. Our present data showed that nanomolar concentrations of MEHP can trigger the proliferation, while not invasion, of cervical cancer HeLa and SiHa cells, which was confirmed by the results that MEHP can also increase the expression of proliferating cell nuclear antigen (PCNA). MEHP treatment can increase the phosphorylation and nuclear localization of Akt, while had no effect on the activation of ERK1/2 or p65. Targeted inhibition of Akt via its specific siRNA or inhibitor can reverse MEHP induced cell proliferation. In addition, the inhibitor of G protein coupled estrogen receptor (GPER), while not estrogen receptor α (ERα), can abolish MEHP induced phosphorylation of Akt and cell proliferation, suggesting that GPER is involved in MEHP induced activation of Akt. Collectively, our data showed that MEHP can trigger the progression of cervical cancer via activation of GPER/Akt. It suggested that MEHP exposure is also an important risk factor for development and progression of cervical cancers.

KEYWORDS:

Akt; Cervical cancer; GPER; MEHP; Proliferation

PMID:
29382535
DOI:
10.1016/j.ejphar.2018.01.040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center