Objective: To investigate the effect of sodium phenylbutyrate (SPB) in modulating docetaxel resistance in human prostate cancer cells in vitro.
Methods: A PC3/docetaxel-resistant human prostate cancer cell line PC3/DTX was induced and examined for proliferation, viability, and cell inhibition rate in the presence of SPB. The concentration of concentration of docetaxel required to kill 50% of PC3/DTX cells incubated with 0, 1, 2, and 4 mmol/L SPB was determined using MTT assay. Cell apoptosis rate was analyzed with flow cytometry and the cellular expressions of p21, cyclin D1 and survivin proteins were detected using Western blotting.
Results: Treatment of PC3/DTX cells with 0, 1, 2, and 4 mmol/L of SPB for 48 h resulted in cell viabilities of (99.85∓2.69)%, (84.68∓3.87)%, (68.65∓4.54)% and (43.54∓5.69)%, and cell inhibition rates of (10.69∓3.65)%, (25.78∓4.58)%, (54.68∓3.98)% and (69.84∓6.54)%, respectively (P<0.05). The concentration of docetaxel required to kill 50% of PC3/DTX cells cultured in the presence of with 0, 1, 2, and 4 mmol/L SPB was 135.98∓2.69, 109.65∓3.87, 87.65∓3.84 and 64.62∓2.98 nmol/L, respectively (P<0.05), and the cell apoptosis rates were (7.2∓0.8)%, (10.2∓0.9)%, (19.8∓2.1)% and (27.4∓2.5)%, respectively. SPB treatment promoted the protein expression of p21 and suppressed the expressions of cyclin D1 and survivin in PC3/DTX cells.
Conclusion: SPB can affect the expressions of p21, cyclin D1, and survivin in PC3/DTX cells and increase the sensitivity to the drug-resistant cells to docetaxel.
目的: 研究苯丁酸钠对前列腺癌多烯紫杉醇耐药细胞株的增值抑制与凋亡诱导作用，并探讨其作用机制。
方法: 构建多烯紫杉醇耐药前列腺癌PC3细胞株（PC3/DTX），采用0、1、2、4 mmol/L的苯丁酸钠处理PC3/DTX，MTT检测细胞增殖、细胞活力以及抑制率，计算不同浓度苯丁酸钠处理后各组多烯紫杉醇对PC3/DTX细胞的半致死浓度（IC50）；流式细胞仪检测不同处理组细胞凋亡水平；Western blot检测p21、Cyclin D1与Survivin的表达水平。
结果: 0、1、2、4 mmol/L的苯丁酸钠处理PC3/DTX细胞48 h后，细胞存活率分别是（99.85±2.69）%，（84.68±3.87）%，（68.65±4.54）%和（43.54±5.69）%（P < 0.05）；抑制率分别是（10.69±3.65）%，（5.78±4.58）2%，（54.68±3.98）%和（69.84±6.54）%（P < 0.05）；多烯紫杉醇对各处理组细胞的IC50分别为135.98±2.69、109.65±3.87、87.65±3.84、64.62±2.98 nmol/L（P < 0.05）；细胞的凋亡率分别为（7.20±0.80）%，（10.20±0.90）%，（19.80±2.10）%和（27.40±2.50）%（P < 0.05）；Western blot显示苯丁酸钠促进p21蛋白的表达，抑制Cyclin D1与Survivin蛋白的表达。
结论: 苯丁酸钠可以增加前列腺癌耐药细胞株对多烯紫杉醇的药敏性，并影响前列腺癌耐药细胞株p21、Cyclin D1与Survivin蛋白的表达量。