THE HDAC INHIBITOR SODIUM PHENYLBUTYRATE ENHANCES THE CYTOTOXICITY INDUCED BY 5-FLUOROURACIL, OXALIPLATIN, AND IRINOTECAN IN COLORECTAL CANCER CELL LINES
Keywords:Colorectal cancer, Histone deacetylase inhibitor, Sodium phenylbutyrate, Adjuvant chemotherapy
Objective: The main objective of this study was to evaluate the ability of sodium phenylbutyrate (NaPB) to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53.
Methods: The antiproliferative effect of NaPB alone or in combination with 5-fluorouracil, oxaliplatin, or irinotecan in HCT-116 and HT-29 colorectal cancer cell lines was investigated using the MTT cell proliferation assay. IC50 values were calculated using Compusyn Software 1.0 (Combosyn Inc.). Synergy values (R) were calculated using the ratio of IC50 of each primary drug alone divided by combination IC50s. For each two pairs of experiments, student's t-test was used for analysis. In combination studies, one-way ANOVA test; Tukey post-hoc testing was performed using R 3.3.2 software. P-value<0.05 was considered significant.
Results: NaPB inhibited the growth of HCT-116 and HT-29 cell lines in a dose-dependent manner (IC50s 4.7 mmol, and 10.1 mmol, respectively). HT-29 cell lines (mutant p53) were more sensitive to NaPB at low concentrations (<4 mmol). Moreover, the addition of NaPB to HCT-116 and HT-29 with 5-fluorouracil, oxaliplatin, or irinotecan synergistically induced the antiproliferative effect (R>1.6, p-value<0.05).
Conclusion: NaPB enhanced the cytotoxicity of conventional chemotherapy against colorectal cancer cell lines harboring wild-type or mutant p53. Thus NaPB is a promising potential adjuvant chemotherapy in colorectal cancer.
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