This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lu, L. Articles by Luo, W. PubMed PubMed Citation Articles by Lu, L. Articles by Luo, W.

Research Articles: Therapeutics, Targets, and Development

Vitamin D₃ analogue EB1089 inhibits the proliferation of human laryngeal squamous carcinoma cells via p57

¹ Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital and ² Department of Occupational and Environmental Health Sciences, Fourth Military Medical University, Xi'an, People's Republic of China

Requests for reprints: Wenjing Luo, Department of Occupational and Environmental Health Sciences, Fourth Military Medical University, 17 Changlexi Road, Xi'an, Shaanxi 710032, People's Republic of China. Phone: 86-29-84774863; Fax: 86-29-84774863. E-mail: luowenj{at}fmmu.edu.cn

Abstract

The objective of this study is to evaluate the role of the cyclin-dependent kinase inhibitor p57 in EB1089-inhibited proliferation of human laryngeal squamous carcinoma cells (HEp-2). HEp-2 cells were treated with the vitamin D₃ analogue EB1089 for 48 h and total RNA was extracted for reverse transcription-PCR amplification using primers for the p57 coding sequence. Proteins were detected by Western blot analysis. For interference using silencing RNA (siRNA), HEp-2 cells were transfected with siRNA specific for p57 (siRNA-p57) or a negative control sequence (siRNA-con) followed by treatment with 10 nmol/L EB1089. The effects of EB1089 on cell proliferation were evaluated by 5-bromo-2'-deoxyuridine incorporation and `3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay. Cell death and cell cycle dynamics were monitored using flow cytometry. EB1089 significantly inhibited HEp-2 cell proliferation and increased p57 mRNA and protein levels; this was blocked by siRNA-p57 but not by siRNA-con. The EB1089-induced suppression of HEp-2 cell proliferation recovered to near-normal levels with siRNA-p57 transfection. EB1089 inhibits the proliferation of HEp-2 cells and p57 plays an important role in this. [Mol Cancer Ther 2008;7(5):1268–74]

Grant support: National Natural Science Foundation of China grants 30100148, 30471434, and 30571545.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 10/23/07; revised 2/15/08; accepted 2/17/08.