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Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2010 Jun;71(3):162–172. doi: 10.1016/j.curtheres.2010.06.002

Effects of a histone deacetylase inhibitor, sodium butyrate, on 53-kDa protein expression and sensitivity to anticancer drugs of pancreatic cancer cells

Masaki Kitazono 1,*, Hiroyuki Shinchi 1, Sumiya Ishigami 1, Shinichi Ueno 1, Shoji Natsugoe 1
PMCID: PMC3967367  PMID: 24683262

Abstract

Background: Several tumor-suppressor genes, such as 53-kDa protein (p53), are inactivated in some pancreatic cancers. The lack of a functional p53 has been proposed to be a component of resistance to chemotherapy, resulting in the inhibition of apoptosis. Therefore, reintroduction of wild-type p53 is a commonly used gene therapy strategy for the treatment of various types of cancer, including pancreatic cancer.

Objective: The aim of this study was to examine the ability of the histone deacetylase inhibitor, sodium butyrate (NaB), to modulate the expression of p53.

Methods: Five human pancreatic carcinoma cell lines (SW-1990, BxPC-3, PANC-1, MIA PaCa-2, JHP-1) were utilized. Two of the cell lines (SW-1990 and JHP-1) lacked p53 expression, as determined by Western blot analysis, and were investigated further. Expression of p53 was determined by densitometry of all bands present in the Western blot. Drug sensitivity was measured with a tetrazolium-based assay by exposing the cells to graded concentrations of NaB and/or anticancer drugs (cisplatin, fluorouracil, SN-38, and paclitaxel). Apoptosis was observed using gel electrophoresis.

Results: In the SW-1990 and JHP-1 cell lines, use of 1 mM NaB was found to induce histone acetylation and p53 expression compared with those not treated with NaB (P = 0.01 and P = 0.018, respectively). Sensitivity to cisplatin (P = 0.021), fluorouracil (P = 0.046), and SN-38 (P = 0.039) was significantly enhanced by NaB treatment compared with nontreatment. However, sensitivity to paclitaxel was not significantly different between untreated and NaB-treated cells. A higher frequency of apoptosis was observed in NaB-treated cells compared with that of control cells.

Conclusion: This in vitro study found that NaB induced p53 expression in 2 pancreatic cancer cell lines (SW-1990 and JHP-1). Moreover, NaB acted on a biochemical modulator for antieuplastic therapy. Future research is necessary to assess the value of these findings.

Key words: sodium butyrate, 53-kDa protein expression, human pancreatic carcinoma cell lines, in vitro

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