Inhibition of survivin reduces HIF-1α, TGF-β1 and TFE3 in salivary adenoid cystic carcinoma

Yu-Fan Wang; Si-Rui Ma; Wei-Ming Wang; Cong-Fa Huang; Zhi-Li Zhao; Bing Liu; Wen-Feng Zhang; Yi-Fang Zhao; Lu Zhang; Zhi-Jun Sun

doi:10.1371/journal.pone.0114051

Inhibition of survivin reduces HIF-1α, TGF-β1 and TFE3 in salivary adenoid cystic carcinoma

PLoS One. 2014 Dec 8;9(12):e114051. doi: 10.1371/journal.pone.0114051. eCollection 2014.

Authors

Affiliations

¹ The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
² Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
³ The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Abstract

In the present study, we explored the expression and correlation of survivin with HIF-1α, TGF-β1 and TFE3 in adenoid cystic carcinoma (AdCC). The expression of survivin, HIF-1α, TGF-β1 and TFE3 was assessed by immunohistochemical staining of a tissue microarray containing tissue samples of normal salivary gland (NSG), pleomorphic adenoma (PA) and AdCC. Correlation analysis of these proteins revealed that increased survivin expression was associated with the overexpression of HIF-1α (P<0.001, r = 0.5599), TGF-β1 (P<0.001, r = 0.6616) and TFE3 (P<0.001, r = 0.7747). The expression of survivin, HIF-1α, TGF-β1 and TFE3 was not correlated with the pathological type of human AdCC (P>0.05). Selective inhibition of survivin by YM155 and siRNA significantly reduced human SACC-83 cell proliferation, with the corresponding decrease in expression of HIF-1α, TGF-β1 and TFE3. The data indicate that the overexpression of survivin in AdCC is related to HIF-1α, TGF-β1 and TFE3. We hypothesize from these findings that the inhibition of survivin may be a novel strategy for neoadjuvant chemotherapeutic and radiosensitive treatment of AdCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
Carcinoma, Adenoid Cystic / genetics
Carcinoma, Adenoid Cystic / metabolism*
Carcinoma, Adenoid Cystic / pathology
Case-Control Studies
Cell Line, Tumor
Cluster Analysis
Gene Expression
Gene Expression Regulation, Neoplastic / drug effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Imidazoles / pharmacology
Immunohistochemistry
Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
Inhibitor of Apoptosis Proteins / genetics
Inhibitor of Apoptosis Proteins / metabolism
Naphthoquinones / pharmacology
Neoplasm Grading
Salivary Gland Neoplasms / genetics
Salivary Gland Neoplasms / metabolism*
Salivary Gland Neoplasms / pathology
Survivin
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / metabolism*

Substances

BIRC5 protein, human
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Hypoxia-Inducible Factor 1, alpha Subunit
Imidazoles
Inhibitor of Apoptosis Proteins
Naphthoquinones
Survivin
TFE3 protein, human
Transforming Growth Factor beta1
sepantronium

Grants and funding

This work was funded by National Natural Science Foundation of China (81072203, 81272963) to Z.-J. Sun, (81371106) to L. Zhang, (81272946) to W.-F. Zhang, and (81170977) to Y.-F. Zhao. Z.-J. Sun supported by program for new century excellent talents in university (NCET-13-0439), ministry of education of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.