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Open Access Research article

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells

Xing-dong Xu1, Lan Yang1, Li-yun Zheng2, Yan-yan Pan3, Zhi-fei Cao3, Zhi-qing Zhang4, Quan-sheng Zhou3, Bo Yang1* and Cong Cao4*

Author Affiliations

1 Department of General Surgery, the Third Hospital affiliated to Soochow University, Changzhou City 213003, Jiangsu, China

2 Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, China

3 Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, Jiangsu, China

4 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou 215021, Jiangsu, China

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BMC Cancer 2014, 14:373  doi:10.1186/1471-2407-14-373

Published: 27 May 2014

Abstract

Background

Pancreatic cancer is one of the most aggressive human malignancies with a extremely low 5-year survival rate. Hence, the search for more effective anti-pancreatic cancer agents is urgent.

Methods

PaTu8988 pancreatic cancer cells were treated with different concentrations of suberoylanilide hydroxamic acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and Western blots.

Results

Here, we reported that SAHA, a histone deacetylase inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic cancer cell survival, proliferation, migration and VM. SAHA dose-dependently inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 ± 0. 7 μM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin-B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988 cell in vitro migration and cell-dominant tube formation or VM, which was accompanied by semaphorin-4D (Sema-4D) and integrin-β5 down-regulation. Our evidences showed that Akt activation might be important for Sema-4D expression in PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with Akt inhibition.

Conclusions

This study is among the first to report the VM formation in cultured human pancreatic cancer cells. And we provided strong evidence to suggest that SAHA executes significant anti-VM efficiency in the progressive pancreatic cancer cells. Thus, SAHA could be further investigated as a promising anti-pancreatic cancer agent.

Keywords:
Pancreatic cancer; SAHA; Vasculogenic mimicry; Proliferation and apoptosis