国际肿瘤学杂志

国际肿瘤学杂志 ›› 2017, Vol. 44 ›› Issue (5): 327-331.doi: 10.3760/cma.j.issn.1673422X.2017.05.002

• 论著 • 上一篇    下一篇

番茄红素对人肝癌细胞增殖和凋亡的影响及其机制 

杨丽萍, 赵孟雷, 凌书建   

  1. 056001河北省邯郸市中心医院重症医学科（杨丽萍），普外三科（赵孟雷），烧伤整形科（凌书建）
  • 出版日期:2017-05-08 发布日期:2017-04-19
  • 通讯作者: 杨丽萍，Email: 964889005@qq.com E-mail:964889005@qq.com

Effects and mechanism of lycopene on the proliferation and apoptosis of human hepatoma cells

Yang Liping, Zhao Menglei, Ling Shujian   

  1. Intensive Care Unit, Handan Central Hospital of Hebei Province, Handan 056001, China
  • Online:2017-05-08 Published:2017-04-19
  • Contact: Yang Liping E-mail:964889005@qq.com

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摘要： 目的研究番茄红素对人肝癌HepG2细胞增殖和凋亡的影响及其机制。方法取对数生长期人肝癌HepG2细胞，分别给予不同浓度番茄红素（5、10、20 μg/ml）和顺铂（40 μg/ml）进行干预，48 h后通过四甲基偶氮唑蓝（MTT）比色法测定细胞增殖抑制率，通过流式细胞术检测细胞周期和细胞凋亡状况，采用Western blotting技术检测Bax、Bcl2、激活型Caspase3蛋白表达。结果干预48 h后，空白对照组人肝癌HepG2细胞增殖抑制率为0，番茄红素（5、10、20 μg/ml）组和顺铂组分别为(21.3±4.2)%、(40.5±7.6)%、(63.8±9.1)%和(37.8±5.9)%，差异有统计学意义（F=37.905，P=0.000）；它们分别与空白对照组比较，差异均具有统计学意义（t=208.124，P=0.000；t=394.637，P=0.000；t=628.592，P=0.000；t=257.168，P=0.000）。番茄红素（10、20 μg/ml）组细胞周期G0G1期比例分别为(54.0±2.9)%、(67.3±3.6)%，与空白对照组(37.9±1.5)%比较，差异有统计学意义（t=4.508，P=0.024；t=10.673，P=0.006）；番茄红素（10、20 μg/ml）组G2M期比例分别为(8.5±0.6)%、(4.7±0.5)%，与空白对照组比较(18.4±0.8)%，差异有统计学意义（t=9.975，P=0.008；t=13.864，P=0.003）。番茄红素组（5、10、20 μg/ml）和顺铂组细胞凋亡指数分别为(19.5±4.8)%、(43.0±9.2)%、(67.6±10.1)%和(36.9±6.8)%，与空白对照组［(3.6±1.7)%］比较均显著升高，差异有统计学意义（t=18.617，P=0.001；t=34.295，P=0.000；t=51.437，P=0.000；t=29.804，P=0.000）。番茄红素（10、20 μg/ml）组和顺铂组Bcl2、Bax表达及Bax/Bcl2比值分别为0.42±0.09、0.43±0.14、1.02±0.39,0.27±0.08、0.76±0.19、2.81±0.85和0.34±0.11、0.31±0.09、0.91±0.40，与空白对照组(0.59±0.17、0.18±0.06、0.31±0.12)比较，Bcl2表达显著下调，差异具有统计学意义（t=4.327，P=0.023；t=11.064，P=0.006；t=5.182，P=0.018），Bax表达显著上调，差异具有统计学意义（t=9.837，P=0.008；t=17.349，P=0.001；t=10.165，P=0.007），Bax/Bcl2比值显著升高，差异均具有统计学意义（t=11.521，P=0.006；t=18.194，P=0.001；t=9.537，P=0.008）。番茄红素（5、10、20 μg/ml）组和顺铂组激活型Caspase3蛋白表达分别为0.25±0.07、0.34±0.11、0.46±0.18和0.17±0.05，与空白对照组(0.08±0.03)比较，差异具有统计学意义（t=8.307，P=0.009；t=13.067，P=0.006；t=16.218，P=0.003；t=5.202，P=0.019）。结论番茄红素能够通过抑制细胞增殖并促进其凋亡而对人肝癌HepG2细胞生长起到一定的抑制作用，其机制可能与番茄红素能够影响细胞周期进程并调节凋亡相关基因蛋白表达有关。

关键词: 肝肿瘤, 细胞增殖, 细胞凋亡, 番茄红素, HepG2细胞

Abstract: ObjectiveTo investigate the effects and mechanism of lycopene on the proliferation and apoptosis of human hepatoma cell HepG2. MethodsThe human HepG2 cells in logarithmic growth phase were treated with lycopene (5, 10, 20 μg/ml) and cisplatin (40 μg/ml). The cellular growth inhibition rate was calculated by methyl thiazolyl tetrazolium (MTT) after 48 h, and cell cycle and apoptosis rate were analyzed by flow cytometry. The expressions of Bax, Bcl2 and cleaved Caspase3 proteins were detected by Western blotting. ResultsAfter 48 h intervention, the cellular growth inhibition rate of human HepG2 cell in blank control group was 0, and in lycopene (5, 10, 20 μg/ml) groups and cisplatin group were (21.3±4.2)%, (40.5±7.6)%, (63.8±9.1)%, (37.8±5.9)%, with significant difference (F=37.905, P=0.000); and compared with blank control group respectively, the differences were statistically significant (t=208.124, P=0.000; t=394.637, P=0.000; t=628.592, P=0.000; t=257.168, P=0.000). The G0G1 phase rates in lycopene (10, 20 μg/ml) groups were (54.0±2.9)% and (67.3±3.6)%, compared with blank control group (37.9±1.5)%, the differences were statistically significant (t=4.508, P=0.024; t=10.673, P=0.006). The G2M phase rates in lycopene (10, 20 μg/ml) groups were (8.5±0.6)% and (4.7±0.5)%, compared with blank control group (18.4±0.8)%, the differences were statistically significant (t=9.975, P=0.008; t=13.864, P=0.003). The apoptosis index (AI) in lycopene (5, 10, 20 μg/ml) groups and cisplatin group were (19.5±4.8)%, (43.0±9.2)%, (67.6±10.1)% and (36.9±6.8)%, compared with blank control group ［(3.6±1.7)%］, the differences were statistically significant (t=18.617, P=0.001; t=34.295, P=0.000; t=51.437, P=0.000; t=29.804, P=0.000). The expressions of Bcl2, Bax and the ratio of Bax/Bcl2 in lycopene (10, 20 μg/ml) groups and cisplatin group were 0.42±0.09, 0.43±0.14, 1.02±0.39; 0.27±0.08, 0.76±0.19, 2.81±0.85; 0.34±0.11, 0.31±0.09, 0.91±0.40, respectively. Compared with blank control group (0.59±0.17, 0.18±0.06, 0.31±0.12), the expressions of Bcl2 were significantly downregulated, and the differences were statistically significant （t=4.327，P=0.023；t=11.064，P=0.006；t=5.182，P=0.018）,  the expressions of Bax were significantly upregulated, and the differences were statistically significant (t=9.837, P=0.008; t=17.349, P=0.001; t=10.165, P=0.007), the ratios of Bax/Bcl2 were significantly increased, and the differences were statistically significant (t=11.521, P=0.006; t=18.194, P=0.001; t=9.537, P=0.008). The expressions of cleaved Caspase3 protein in lycopene (5, 10, 20 μg/ml) groups and cisplatin group were 0.25±0.07, 0.34±0.11, 0.46±0.18 and 0.17±0.05, compared with blank control group (0.08±0.03), the differences were statistically significant (t=8.307, P=0.009; t=13.067, P=0.006; t=16.218, P=0.003; t=5.202, P=0.019). ConclusionLycopene has inhibitive effect on the growth of human HepG2 cells perhaps through inhibiting proliferation and inducing apoptosis, which may be related to its effects of altering the cell cycle and the expressions of apoptosisrelated genes and proteins.

Key words: Liver neoplasms, Cell proliferation, Apoptosis, Lycopene, HepG2 cells