大黄素对荷A549肺癌小鼠肿瘤的疗效及其作用机理研究

Anti-tumor Effect and Mechanism of Emodin on Nude Mice Bearing Lung Cancer A549 Cells

目的探讨大黄素(emodin)对荷A549肺癌小鼠肿瘤生长的影响及抗肿瘤机制。方法以PBS作为阴性对照,顺铂作为阳性对照,分析大黄素对肺癌细胞A549增殖和凋亡的影响;建立荷A549肺癌小鼠模型,随机分为模型组、大黄素组和顺铂组,大黄素组给予腹腔注射大黄素10 mg·kg-1,顺铂组给予腹腔注射顺铂5mg·kg-1,治疗30 d,观察各组小鼠肿瘤生长、生存率和体质量的变化。采用Western blot分析每组小鼠肿瘤组织中增殖细胞核抗原(PCNA)和Caspase-3蛋白质的变化。结果在细胞水平上,与PBS组比较,大黄素组和顺铂组能显著抑制肺癌细胞A549的增殖,并促进肿瘤细胞的凋亡,差异有统计学意义(P<0.05)。大黄素组、顺铂组肿瘤生长较模型组明显被抑制,而生存率较模型组明显增加(P<0.05)。顺铂组小鼠体质量较大黄素组和模型组明显下降(P<0.05),而大黄素组与模型组小鼠体质量比较无统计学意义(P>0.05)。大黄素组和顺铂组小鼠肿瘤组织中PCNA的表达水平较模型组明显下降,而Caspase-3蛋白水平较模型组明显升高,差异有统计学意义(P<0.05)。结论大黄素能抑制A549细胞的生长,促进肿瘤细胞凋亡,具有明显抑制肿瘤组织生长作用,且毒副作用较小。

Objective To investigate anti-tumor effect and mechanism of emodin on nude mice bearing lung cancer A549 cells. Methods The proliferation and apoptosis of A549 lung cancer cells in vitro were analyzed by MTT and flow cytometry, with PBS as negative control and with cisplatin as the positive control. In the in-vivo experiment, 45 mice bearing A549 lung cancer were randomly divided into PBS group, emodin group （10 mg/kg by intraperitoneal injection）and cisplatin group（5 mg/kg by intraperitoneal injection）. After treatment for 30 days, the tumor growth, survival rate and body weight were analyzed in the three groups. The proliferating cell nuclear antigen （PCNA） and Caspase-3 protein expression levels in tumor tissues were analyzed by Western blotting method. Results Compared with PBS, emodin and cisplatin significantly inhibited the proliferation of A549 lung cancer cells and promoted the apoptosis of tumor cells, and there was statistically significant difference at the cellular level（P 〈 0.05）. Compared with PBS group, the tumor growth in emodin group and cisplatin group was significantly inhibited （P 〈 0.05）, while the survival rate in emodin group and cisplatin group significantly increased （P 〈 0.05 ）. Compared with emodin group and PBS control group, the body weight of mice in cisplatin group was significantly decreased （P 〈 0.05）, but the difference of body weight was not statistically significant between emodin group and PBS group （P 〉 0.05）. The PCNA expression level in emodin group and cisplatin group was lower, while the level of Caspase-3 protein was significantly higher than the PBS control group, the difference being statistically significant（P 〈 0.05）. Conclusion Emodin can inhibit the growth of A549 cells and promote the apoptosis of tumor cells, inhibit the growth of tumor and have fewer side effects. It is expected to become a new anticancer drug.