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Enhanced Expression of Genes Associated with Invasion and Metastasis in Trichostatin A Resistance Pancreatic Cancer Cells Line
Liu Biao1, Chen Xiaoqian2, Zhang Cui2, Wang Benquan1, Bai Yongheng2, Wang Silu2,Jin Rong1, Zhou Mengtao1, Chen Bicheng1,2*
1Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China;2Laboratory of Surgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China
Abstract: The aim of this study was to investigate the change of invasion ability on PANC-1. PANC-1 cells line was treated with 0.1~0.2 μmol/L TSA for 24 hours. TSA-resistant pancreatic cancer cells line (PANC-1-TSA) was established by drug concentration step-elevation method. The 24 h IC50 of PANC-1 and PANC-1-TSA was (0.51±0.09) μmol/L and (78±5) μmol/L respectively， and the resistance index of PANC-1-TSA was 153. Transwell array experiment showed that PANC-1-TSA has stronger capability for invasion and metastasis than PANC-1 cells， while there was no significant difference in the 0.1 μmol/L TSA group. In RT-qPCR assessments， the expressions of MMPs and TIMPs mRNA were all up-regulated in PANC-1-TSA， and the MMPs mRNA increased much more significantly. We also found that PANC-1-TSA cells suffered morphological alteration from epithelial morphology to mesenchymal morphology. Both the RT-qPCR and Western blot experiments confirmed that the PANC-1 cells line was suffered EMT during the process of forming drug resistance， with up-regulation of mesenchymal markers and downregulation of epithelial markers. This paper demonstrated that TSA-resistant cells line had stronger capability for invasion and metastasis and much more aggressive than PANC-1. EMT might contribute to PANC-1-TSA cells line aggression.
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