Chang Wen-Tsan, Lin Hui-Li, Chang Kee-Lung, Ker Chen-Guo, Huang Meng-Chuan, Chen Jong-Shyone, Kuo Kung-Kai, Chen Ying-Lin, Lee King-Teh
Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Hepatogastroenterology. 2010 Jan-Feb;57(97):107-13.
BACKGROUND/AIMS: The use of chemotherapy in hepatocellular carcinoma is still controversial. The aim of this study was to investigate whether the combined use of epirubicin and progesterone has a synergistic effect on cell proliferation and apoptosis in HepG2 cells.
Different concentrations of epirubicin (0.1 microg/ml, 0.25 microg/ml and 0.5microg/ml) or progesterone (12.5 microM, 25 microM and 50 microM) were added to HepG2 cells either alone or in combinations consisting of different concentrations of the two. Their effects on HepG2 cells were studied by (1) XTT assay for analysis of cell proliferation, (2) 3H-Thymidine incorporation for DNA synthesis, (3) annexin V-FITC/ propidium iodide (PI) flowcytometery for cell apoptosis, (4) flowcytometry for cell cycle distributions, and (5) reverse transcription-polymerase chain reaction for expression of cell cycle modulator, cyclin D1.
50 microM progesterone increased both the cytotoxic and apoptotic effects of 0.1 microg/ml epirubicin on HepG2 cells at 48 hr culture due to 50 microM progesterone accumulated cells in S phase of the cell cycle and subsequently reduced cyclin D1 expression. These effects on HepG2 cells induced by this combination were comparable to those induced by 0.5 microg/ml epirubicin alone.
In vitro, progesterone can increase the cytotoxicity and apoptosis induced by epirubicin on HepG2 cells.
背景/目的：化疗在肝细胞癌中的应用仍存在争议。本研究旨在探讨表柔比星与孕酮联合使用对HepG2细胞增殖和凋亡是否具有协同作用。
将不同浓度的表柔比星（0.1微克/毫升、0.25微克/毫升和0.5微克/毫升）或孕酮（12.5微摩尔/升、25微摩尔/升和50微摩尔/升）单独或按不同浓度组合添加到HepG2细胞中。通过以下方法研究它们对HepG2细胞的影响：（1）采用XTT法分析细胞增殖；（2）采用3H-胸腺嘧啶核苷掺入法检测DNA合成；（3）采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶（PI）流式细胞术检测细胞凋亡；（4）采用流式细胞术分析细胞周期分布；（5）采用逆转录-聚合酶链反应检测细胞周期调节因子细胞周期蛋白D1的表达。
在培养48小时时，50微摩尔/升孕酮增强了0.1微克/毫升表柔比星对HepG2细胞的细胞毒性和凋亡作用，这是因为50微摩尔/升孕酮使细胞在细胞周期的S期积累，随后降低了细胞周期蛋白D1的表达。该联合用药对HepG2细胞的这些作用与单独使用0.5微克/毫升表柔比星诱导的作用相当。
在体外，孕酮可增强表柔比星对HepG2细胞的细胞毒性和凋亡作用。
