Trichostatin A Affects Breast Cancer Cell Viability by Modulating Fhit and Survivin Expression

Objective: Investigate the effects of TSA on MCF-7 cell growth in vitro and the expressions of fragile HiT (Fhit) and Survivin gene in human breast cancer cell strain MCF-7. Methods: Cultured cells were divided into control group and TSA groups, and treated with DMSO and different concentration of TSA (50, 100, 200, 500nmol/L) respectively. Then the cell activity was observed by try pan blue stain assay and the transcription level of Fhit and Survivin were analyzed by using real-time PCR. The change of Fhit protein was analyzed by western bolt. Results: The proliferation of breast cancer cell MCF-7 was inhibited significantly after culture with TSA. TSA inhibited the breast cancer cell growth in dose-dependent and time-dependent manners. The expression of Fhit mRNA and protein were all increased significantly (3.12 vs 1, P

I. Introduction

Breast cancer is one of common cancers in women in worldwide. The genesis of breast cancer is regulated by tumor gene and tumor suppressor gene. Fhit gene is a kind of tumor suppressor gene; the protein was expressed in all kinds of tissue cells, and suppresses the growth of tumor cell by inducing tumor cell apoptosis and adjusting cell cycle[1]. The Fhit aberrance has been found in many types of breast cancer, which may be the main reason of oncogenesis of breast cancer tumor [2], [3]. We know that epigenetic modifications involve in cytosine methylation and histone covalent modifications, which effect the expression of many genes[4]. Histone acetylation is regulated by acetyltransferases and histone deacetylases (HDACs)[5]. Trichostatin (TSA) is a kind of HDAC inhibitor which cause growth blocked, differentiation or apoptosis of cells, and TSA with or without other drugs were preclinical studied in pancreatic carcinoma, gastric cancer, and oophoroma [6]–[8]. In this paper, we detected the effects of TSA on the growth of mammary adenocarcinoma cell and the expression of Fhit, to conform the role of TSA. Further, the transcription of Survivin was detected as well.