大黄素治疗裸鼠胰腺癌肝转移瘤的实验研究

Inhibitory Effect of Emodin on Hepatic Metastasis of Human Pancreatic Carcinoma in Nude Mice

目的观察大黄素及其脂质体对裸鼠胰腺癌肝转移模型影响及作用机制。方法建立裸鼠胰腺癌肝转移模型,随机分为对照组、吉西他滨组、实验Ⅰ组、实验Ⅱ组和实验Ⅲ组,每组10只,分别经脾脏注射给予10%葡萄糖、吉西他滨100mg/kg、大黄素10mg/kg、大黄素脂质体5mg/kg和大黄素脂质体10mg/kg。观察各组荷瘤裸鼠肝转移瘤生长情况,免疫组织化学法检测肿瘤组织Ki-67和CD-34表达,Tunel法检测肿瘤组织细胞凋亡,Western blotting法检测肿瘤组织MMP-2和MMP-9表达水平。结果与对照组比较,吉西他滨组、实验Ⅰ、Ⅱ、Ⅲ组肝转移瘤生长明显抑制(P均<0.05);与实验Ⅰ、Ⅱ组比较,实验Ⅲ组肿瘤缩小更明显(P<0.05);实验Ⅲ组瘤重与吉西他滨组比较,差异无统计学意义(P>0.05);实验Ⅰ、Ⅱ、Ⅲ组肿瘤组织Ki-67、CD34、MMP-2和MMP-9表达较对照组均明显降低(P均<0.05),而凋亡细胞明显增加(P均<0.05)。结论大黄素及其脂质体均有抗裸鼠胰腺癌肝转移瘤的作用,但后者作用更为明显,其机制可能与抑制胰腺癌组织MMP-2和MMP-9表达有关。

Objective To investigate the anti-tumor effect of free emodin and liposome emodin on hepatic metas-tasis of human pancreatic carcinoma in nude mice. Methods After the model of hepatic metastasis of human pan-creatic carcinoma was established in mice, the mice were randomized into 5 groups （n=10）, receiving 10% glucose, gemcitabine（100 mg/kg）, free emodin（10 mg/kg）, and liposomal emodin（5 and 10 mg/kg）via spleen injection in each group. The hepatic metastatic foci of pancreatic tumor weight and inhibition rate were evaluated after the mice were sacrificed. Immunohistochemistry（IHC） was used to detect the positive expression of Ki-67 and CD34 in tumors. The Tunel test kit was used to explore cellular apoptosis in tumor tissue. Expression of MMP-2 and MMP-9 were de-tected by Western blotting. Results Administration of gemcitabine, liposomal emodin and free emodin significantly decreased tumor weight as compared to untreated controls （P＆lt;0.05）; administration of liposomal emodin resulted in a substantial delay of tumor growth as compared to free emodin at the same dose （P＆lt;0.05）, but did not result in a significant difference as compared to gemcitabine group （P＆gt;0.05）. The positive expression of Ki-67 and CD34 in the tumors of liposomal emodin groups were significantly lower than those in control group （P＆lt;0.05）. Apoptosis occurred more frequently in liposomal emodin group than in control group （P＆lt;0.05）. Conclusion Emodin has the anti-tumor effect on hepatic metastasis of pancreatic tumor and the effect is more obvious in liposomal emodin than in free e-modin. The underlying mechanism may partially be through down-regulation of MMP-2 and MMP-9.