MEHP promotes the proliferation of cervical cancer via GPER mediated activation of Akt.
Eur J Pharmacol
; 824: 11-16, 2018 Apr 05.
Article
in En
| MEDLINE
| ID: mdl-29382535
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phthalic Acids
/
Receptors, Estrogen
/
Uterine Cervical Neoplasms
/
Receptors, G-Protein-Coupled
/
Proto-Oncogene Proteins c-akt
Type of study:
Risk_factors_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Eur J Pharmacol
Year:
2018
Document type:
Article