摘要
目的研究番茄红素（LP）对体外人非小细胞肺癌细胞A549增殖、凋亡及荷肺癌裸小鼠移植瘤生长的影响。方法体外细胞实验：体外培养并取处于对数生长期的A549细胞进行分组，分别给予培养液（空白对照组）、不同浓度LP（5、10、20mg／L）及顺铂（40mg／L）进行干预，每组10个复孔；药物干预48h后观察各组细胞形态，检测细胞周期，测定细胞增殖抑制率，观察细胞凋亡状况。体内动物实验：通过右侧腹股沟区皮下接种A549细胞建立荷肺癌裸小鼠模型并分组，分别腹腔注射生理盐水（模型对照组）、不同浓度LP[5、10、20mg／（kg·d）]和顺铂[2rag／（kg·d）]进行干预治疗，各20只；计算抑瘤率，观察肿瘤组织细胞形态和细胞凋亡状况，测定B细胞淋巴瘤／白血病2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）、激活型半胱氨酸天冬氨酸蛋白酶3（caspase-3）蛋白表达。结果体外细胞实验：空白对照组A549细胞贴壁生长、增殖迅速，各剂量LP组、顺铂组A549细胞生长脱壁、形态变圆、细胞间隙松散；与空白对照组比较，各剂量LP组、顺铂组细胞周期G0～G1期比例升高，细胞增殖抑制率升高，细胞凋亡率升高，差异均有统计学意义（P值均〈0．05）。体内动物实验：与模型对照组比较，10、20mg／（kg·d）LP组抑瘤率升高，肿瘤组织呈现片状坏死、细胞皱缩等病变，细胞凋亡指数升高，肿瘤组织凋亡相关蛋白Bcl-2表达下调，Bax表达上调且Bax／Bcl-2比值升高，激活型caspase-3蛋白表达上调，差异有统计学意义（P〈0．05）。结论LP对体外肺癌细胞生长和体内肺癌移植瘤生长均具有一定的抑制作用，机制可能与LP阻滞肺癌细胞周期、促进肺癌细胞凋亡有关。
Objective To investigate the effects of lycopene （LP） on the proliferation, apoptosis of human non small cell lung cancer A549 cells in vitro and transplanted tumor growth in lung cancer- bearing nude mice. Methods Cell experiments in vitro ： the A549 cells were cultured in vitro and the cells in logarithmic growth phase were grouped into blank group （culture medium）, LP （5, 10, 20 mg/L） groups and eisplatin （40 mg/L） group, n ： 10. 48 h after drug intewention, the cell morphology and apoptosis were observed; the cell cycle and the cellular growth inhibition rate were detected. Animal experiments in vivo：the nude mice models bearing lung cancer were made by injecting inoculation human lung cell line A549 at right groin area and grouped into model group, LP [5,10, 20 mg/（kg·d）] groups and cisplatin 2 mg/（kg·d） group. The inhibition rate was calculated;the histopathological changes and the tumor cells apoptosis were observed, the expression of B-cell lymphoma/leukemia-2 （Bcl-2）, Bax, cleved caspase 3 were detected. Results Cell experiments in vitro： The A549 cells in blank group showed adherent growth and proliferation rapidly, while the cells in LP groups and cisplatin group showed that the proliferation was inhibited, the cell number was significantly reduced, and showing retraction, loose and off phenomenon. Compared with blank group, the morphological of LP groups was abnormalities, the percent in G0-G1 phase of cell cycle were increased, the cellular growth inhibition rate in LP groups and cisplatin group were significantly increased, the apoptosis rate was significantly increased （all P 〈 0.05）. Animal experiments in vivo： Compared with model group, the inhibition rate of 10, 20 mg/（kg·d） LP were significantly increased; necrosis presentation, tumor cell shrinkage and other pathological morphological changes appeared in 10,20 mg/（kg·d） LP groups;the expression of Bcl 2 was significantly decreased, the expression of Bax was significantly increased, the ratio of Bax/Bcl-2 were significantly increased, the expression of eleved caspase-3 protein were significantly increased; all of the difference above were significant （ P 〈0.05）. Conclusions LP can effectively inhibit the growth of lung cancer cells in vitro and the growth of transplanted tumor in vivo, which perhaps related to its effects of altering the lung cancer cell cycle and promoting lung cancer cell apoptosis.
作者
王贵刚
董跃华
杨燕君
Wang Guigang;Dong Yuehua;Yang Yanjun(Department of Thoracic Surgery,the First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China)
出处
《国际呼吸杂志》
2018年第18期1367-1372,共6页
International Journal of Respiration
关键词
番茄红素
肺癌
细胞周期
抑瘤率
细胞凋亡
Lycopene
Lung cancer
Cell cycle
Growth inhibition rate
Apoptosis
