摘要
目的 :探讨丁酸钠 (NaB)对人卵巢癌KK细胞和子宫内膜癌HHUA细胞生长的影响和分子机制及其作为新型抗肿瘤药物的潜力。方法 :NaB作用于体外培养的人卵巢癌细胞系KK和人子宫内膜癌细胞系HHUA ,用HE染色及DNA荧光染色观察细胞形态学及染色质改变 ,用流式细胞仪定量分析细胞周期分布及细胞凋亡 ,用2 %琼脂糖凝胶电泳检测DNAladder ,用Westernblot分析PARP、Fas、Bcl 2和Bax蛋白表达。结果 :NaB处理两种细胞 2 4小时后 ,低浓度 (≤ 2mol/L)出现细胞周期停止 ,G1期细胞百分率达 70 %以上 ;中浓度 (4mol/L和 10mol/L)出现典型凋亡细胞的形态学和染色质改变 ,高浓度 (>10mol/L)则引起细胞坏死。Westernblot分析显示NaB能上调HHUA细胞Fas蛋白表达 ,而Bcl 2和Bax蛋白表达水平不变。结论 :NaB通过诱导细胞周期阻滞和细胞凋亡而抑制HHUA和KK细胞生长 ,浓度不同细胞的反应性也不同 ,低浓度诱导细胞周期G1期阻滞 ,中浓度诱导细胞凋亡 ,NaB对细胞生长的抑制作用具有药物浓度和时间依赖关系 ,其诱导HHUA细胞凋亡的机制可能与上调Fas蛋白表达有关。
Purpose:To study the growth suppressing effect of sodium butyrate(NaB) on human ovarian carcinoma KK cells and endometrial carcinoma HHUA cells and its mechanism, as well as its potential as a new antitumor agent. Methods:Human endometrial carcinoma cell line HHUA and ovarian carcinoma cell line KK were cultured in vitro and exposed to sodium butyrate. The changes of morphology and chromatin induced by NaB were investigated by means of HE staining and DNA fluorescent staining, respectively. Cell cycle distribution and apoptosis were quantified by using flow cytometric analysis. Apoptotic degradation of DNA was analyzed by extracting DNA and separated by electrophoresis through a 2% agarose gel. Western blotting analysis was carried out to determine the expression of PARP, Fas, Bax and Bcl 2 proteins.Results:NaB arrested HHUA and KK cells at G 1 phase at the low concentration (≤2 mol/L), after 24 hours treatment. The percentage of G 1 phase was up to 70%. While at the medium concentration (4 mol/L and 10 mol/L), both HHUA and KK cells manifested typical apoptotic morphological and chromatic features. High concentration (≥10 mol/L) caused cell necrosis. NaB could upregulate Fas protein expression in HHUA, whereas the levels of Bcl 2 and Bax proteins remained unchanged. Conclusions:NaB may suppress the growth of HHUA and KK cells through arrest of cell cycle and induction of apoptosis. The responses of cells to NaB vary at the different concentrations. NaB induces cell cycle arrest at low concentration and induces apoptosis at medium concentration. The inhibition of NaB on cell growth is in a time and dose dependent manner. Upregulation of Fas protein may be the mechanism of apoptosis induction in HHUA cells. The effects of NaB on HHUA and KK cell growth suggest that NaB may be a new therapeutic agent in cancer treatment.
出处
《中国癌症杂志》
CAS
CSCD
2002年第3期211-214,276,共5页
China Oncology
基金
山东省卫生科技发展计划项目 (No :2 0 0 1CA2DCB2 )资助
