摘要
目的: 探讨熊去氧胆酸 (UDCA)对肝肿瘤细胞株诱导凋亡及抑制增殖的作用和机制。方法:用四氮唑蓝法、流式细胞术、TUNEL法、Wright Giemsa染色法、电镜及免疫细胞化学等方法,观察UDCA对肝肿瘤细胞株HepG2,BEL7402和正常人肝细胞株L 02的生长活力、细胞凋亡、细胞周期及Bax/bcl 2表达的影响。结果: UDCA对HepG2,BEL7402细胞株生长的抑制作用随药物浓度增高而增强(r2 =0. 96, P<0. 01;r2 =0. 97, P<0. 01;48h)。UDCA对HepG2及BEL7402的IC50分别为0. 92 mmol·L-1, 0. 86 mmol·L-1。UDCA(1. 0mmol·L-1 )对HepG2及BEL7402的凋亡率分别为(42±6) %及 (44±4) %,明显高于对照组(P<0. 01),并且阻滞细胞周期于S期。以UDCA(0. 8mmol·L-1 )处理HepG2 后bcl 2 表达由(24. 3±2. 4) %降低为 (10. 1±1. 6 ) %,Bax表达由(43±5) %升高为 (59±3) % (P<0. 01 );处理BEL7402细胞后bcl 2表达由 (21. 6±1. 8) %降为(11. 6±2. 1) %,Bax表达由 ( 44±4 ) %升高为(59±3) % (P<0. 01)。UDCA对L 02细胞无明显作用。结论: UDCA对HepG2, BEL7402细胞株有显著的抑制增殖及诱导凋亡作用,它可能与UDCA阻滞细胞周期、降低bcl 2和提升Bax的表达有关。
AIM: To investigate the effect of inducing apoptosis and proliferative inhibition on hepatoma cell lines by ursodeoxycholic acid (UDCA), and its mechanisms. METHODS: UDCA effects on cell proliferation, apoptosis, cell cycle and the expression of Bax/bcl-2 genes for two human hepatoma cell lines HepG2 and BEL7402, and normal human hepatic cell line L-02 in vitro were detected by applying MTT assay, flow cytometry, TUNEL (terminal deoxynucleotidyl transferase mediated nick end labeling) assay, Wright-Giemsa staining, electron microscopy and immunocytochemistry. RESULTS: UDCA could strongly inhibit the proliferation of HepG2 and BEL7402 cell lines, and with the concentration of UDCA increasing, the effect of proliferative inhibition would become more obvious(r 2=0.96, P<0.01;r 2=0.97, P<0.01;48 h). The IC 50 responses to HepG2 and BEL7402 were 0.92 mmol·L -1 , 0.86 mmol·L -1 , respectively. The apoptosis rates (UDCA 1.0 mmol·L -1 ) of HepG2 and BEL7402 were (42±6) % and (44± 4) %, respectively with higher significance than that of L-02 (P<0.01). UDCA could arrest cell cycle to S phase. Treated HepG2 with UDCA(0.8 mmol·L -1 ), the expression of bcl-2 decreased from (24.3± 2.4) % to (10.1±1.6) % and the expression of Bax increased from (43±5) % to (59±3) %(P< 0.01), while treated BEL7402, the expression of bcl-2 decreased from (21.6±1.8) % to (11.6± 2.1) %, the expression of Bax increased from (44±4) % to (59±3) %(P<0.01).UDCA had no obvious effect on L-02 cell line. CONCLUSION: UDCA may be selectively inhibit proliferation and induce apoptosis of HepG2 and BEL7402 cell lines by blocking cell cycle and regulating the expression of Bax/bcl-2 genes.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2005年第3期192-196,共5页
Chinese Journal of New Drugs and Clinical Remedies
关键词
肝肿瘤
熊去氧胆酸
细胞凋亡
细胞株
liver neoplasms
ursodeoxycholic acid
apoptosis
cell lines
