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J Obstet Gynaecol Res. 2015 Aug;41(8):1240-5. doi: 10.1111/jog.12691. Epub 2015 Apr 1.

Dopamine D2 receptor blocker thioridazine induces cell death in human uterine cervical carcinoma cell line SiHa.

Author information

1
Laboratory of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

AIM:

The aim of this study was to explore the correlation of dopamine D2 receptor (DRD2) and the development of uterine cervical cancer, and the effect of thioridazine (an antagonist of DRD2) on the SiHa cell line.

MATERIAL AND METHODS:

The expression of DRD2 in tissues was detected with immunohistochemistry. SiHa cells were exposed to different concentrations of thioridazine for 24 h, and then cell viability was determined. After 20-μM thioridazine treatment for 24 h, the protein level of DRD2 in SiHa cells was analyzed by Western blots, apoptosis was detected with the phosphatidylserine externalization and comet assay, and necrosis was detected by measuring high-mobility group box 1 protein (HMGB1).

RESULTS:

The expression of DRD2 gradually increased from normal to cancer tissues (P < 0.01). In vitro, DRD2 blocker thioridazine treatment resulted in death of SiHa cells with the expression of DRD2 significantly regulated down (P < 0.05), and thioridazine significantly induced SiHa apoptosis (P = 0.016) and necrosis (P < 0.01).

CONCLUSION:

Higher DRD2 expression is closely associated with cervical cancer progression. After blocking DRD2, SiHa cell growth is significantly suppressed, indicating that DRD2 may function as a novel tumor marker and a potential therapeutic target for cervical cancer.

KEYWORDS:

SiHa cell; cell death; cervical cancer; dopamine D2 receptor; thioridazine

PMID:
25832589
DOI:
10.1111/jog.12691
[Indexed for MEDLINE]

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