南方红豆杉水提物抑制裸鼠A549肺癌移植瘤生长及其机制研究

目的: 研究南方红豆杉水提物对裸鼠A549肺癌移植瘤生长的抑制作用和机制。 方法: 建立荷A549肺癌移植瘤模型,随机分为对照组、低、中、高剂量南方红豆杉水提物实验组,24 h后以等体积生理盐水及药物灌胃,给药7周,每3 d测移植瘤长短径,绘制移植瘤生长曲线,给药7周后处死裸鼠,取瘤组织,计算抑瘤率,采用Real-time PCR及Western blot方法检测mRNA和蛋白水平。 结果: 南方红豆杉水提物各剂量组均有明显抑瘤效果(P<0.05)。与对照组相比,各实验组移植瘤组织中EGFR及Survivin mRNA水平明显下调(P<0.05),VEGF mRNA水平无明显变化。灰度值之比分析显示:各实验组移植瘤组织中EGFR及VEGF蛋白水平均有下调趋势,但差异无统计学意义,Survivin及p-EGFR蛋白水平明显下调(P<0.05)。 结论: 南方红豆杉水提物对血管生成无明显影响,可能通过抑制Survivin蛋白,抑制EGFR磷酸化,起到抑制移植瘤生长的效果。

Study on inhibitory effect of aqueous extract of Taxus chinensis var. mairei on growth of A549 lung cancer xenografts in nude mice and its mechanism

Objective: To study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) on the growth of A549 lung cancer xenografts in nude mice and its mechanism. Method: The A549 lung cancer xenograft model was established, and then randomly divided into the control group, and low, middle and high dose AETC experiment groups. After 24 hours, they were orally administered with normal saline and drugs of the same volume for seven weeks. The length and width of the xenografts were measured every three days, and the xenograft growth curve was drawn. The nude mice were sacrificed after the administration for seven weeks, and their xenografts were collected to cultivate the anti-tumor rate. Real-time PCR and Western-blot were adopted to detect mRNA and protein levels. Result: All of AETC experiment groups showed a significant anti-tumor effect (P<0.05). Compared with the control group, each experimental group showed notable reduction in EGFR and Survivin mRNA in xenograft tissues (P<0.05), with no significant change in VEGF mRNA level. The analysis on gray value ratio showed that EGFR mRNA were down-regulated (P<0.05) in xenograft tissues in all experimental groups, but with no statistical significance in difference, and Survivin and p-EGFR were significantly down-regulated. Conclusion: AETC has not significant effect on angiogenesis, but may have the inhibitory effect on xenograft growth by inhibiting Survivin protein and EGFR phosphorylation.