摘要
采用噻唑蓝(MTT)法检测稀土化合物柠檬酸镧在1×10-3~5mmo.lL-1浓度范围内对体外培养的人乳腺癌细胞株MCF-7、前列腺癌细胞株PC-3、肝癌细胞株HepG2和宫颈癌细胞株HeLa生长的影响。结果表明,柠檬酸镧对各种癌细胞生长的影响存在浓度依赖性,在实验浓度范围内,低浓度无明显作用特征,高浓度抑制癌细胞生长;不同肿瘤细胞对稀土的响应不同,HeLa细胞相对敏感,其IC50值为(0.16±0.08)mmo.lL-1,而MCF-7细胞为(0.18±0.02)mmol.L-1,PC-3细胞为(1.55±0.45)mmo.lL-1,HepG2细胞为(2.71±0.11)mmol.L-1。进一步以0.15mmol.L-1的柠檬酸镧作用于HeLa细胞,采用Hoechst33258荧光染色、PI单染流式细胞仪检测、AnnexinV-FITC/PI双染色法观察镧对HeLa细胞的毒性作用。结果表明,柠檬酸镧作用24h后,HeLa细胞出现明显的凋亡特征,PI染色流式细胞仪检测可见凋亡峰,细胞周期分析表明sub-G1期细胞显著增加,G0/G1期细胞显著减少(P<0.05),AnnexinV-FITC/PI双染检测细胞凋亡率为(61.65±4.60)%(P<0.05)。上述结果表明柠檬酸镧能诱导癌细胞发生凋亡。以HeLa细胞最灵敏而对HepG2并不敏感,其次序为HeLa>MCF-7>PC-3>HepG2。
The effects of lanthanum citrate ( [ LaCit2 ] ^3- ) on the proliferation and viability of different cancer cell lines were investigated using MTT assay. Those included human breast cancer cell line MCF-7, prostate cancer cell line PC-3, hepatocellular carcinoma cell line HepG2 and cervix epitheloid carcinoma cell line HeLa. The effects of [ LaCit2 ]^ 3- on cancer cells were investigated at a concentration range of 1 × 10^-3-5 mmol·L^-1. Results showed a dose-dependent effect of [ LaCit2]^3- on the growth and viability of different cancer cell lines. [ LaCit2 ]^ 3- inhibited the growth of different cancer cell lines at higher concentrations, but no significant inhibition were observed at lower concentration. It was also found that the effect of [ LaCit2 ]^ 3- on cell growth depended on the cancer cell type. The most potent eytotoxicity of [ LaCit2 ] ^3 - was observed in HeLa ceils. The IC50 value for [ LaC- it2]^3- on HeLa cells was (0.16 ±0.08) mmol.L^-1, while the IC50 values of [ LaCit2 ] ^3- on MCF-7, PC-3 and HepG2 were (0.18 ±0.02) mmol·L^-1, (1.55 ± 0.45) mmol.L^-1 and (2.71 ±0.11) mmol-L^-1, respectively. The methods of Hoechst 33258, PI and Annexin V-FITC/PI staining were used to further elucidate the cytotoxic mechanism of [ LaCit2 ]^ 3-. After treatment with 0.15 mmol .L^-1 [ LaCit2 ]^3- for 24 h, some typical morphological changes associated with apoptosis were detected, and the apoptotic peaks in the cell cycle analysis were measured by flow cytometry. Sub-G1 phase was significantly increased and Go/ G1 cell cycle arrest was observed in the [ LaCit2 ]3- treated cells ( P 〈 0.05 ). The apoptosis rate obtained by Annexin V-FITC/PI double stain was (61.65 ± 4.60) % ( P 〈 0.05 ). Those results showed that the inhibition of [ LaCit2]^ 3- on HeLa cells was related to the induction of cell apoptosis. The HeLa cells were more sensitive than the other cell lines and the HepG2 cells were much less sensitive. The potent cytotoxicity was HeLa 〉 MCF-7 〉 PC-3 〉 HepG2. The mechanism of [ LaCit2 ]^3- induced apoptosis in HeLa cells was currently under study by comparative proteomic approach.
出处
《中国稀土学报》
CAS
CSCD
北大核心
2009年第3期441-446,共6页
Journal of the Chinese Society of Rare Earths
基金
国家自然科学基金重点项目(20637010)资助
关键词
柠檬酸镧
肿瘤细胞
凋亡
稀土
lanthanum citrate
cancer cell
apoptosis
rare earths