大蒜素纳米粒抑制原位移植性肝癌生长的实验研究

Nanoparticles of diallyl trisulfide inhibit the growth of orthotopic transplanted hepatocellular carcinoma

目的:探讨大蒜素聚氰基丙烯酸正丁酯纳米粒(DATS-PBCA-NP)对人肝癌裸鼠原位移植瘤生长的影响及其可能的分子机制。方法:采用在裸鼠肝包膜下接种肝细胞HepG2移植物的方法构建人肝癌裸鼠原位移植瘤模型,并将其分为空白对照组、空白纳米粒组、大蒜素(DATS)注射液组和DATS纳米粒组(DATS-PBCA-NP)进行实验;用药2周后处死实验动物,观察肿瘤体积的变化,计算抑瘤率,采用免疫组化法检测肿瘤组织中的增殖细胞核抗原(PCNA),Western blot检测原位肝癌移植物组织中细胞增殖和凋亡相关蛋白的表达。结果:人肝癌裸鼠原位移植瘤模型构建成功率为100%,DATS纳米粒组平均肿瘤体积明显缩小(P<0.05),免疫组化法和Western blot检测显示,DATS纳米粒组PCNA蛋白表达明显降低(P<0.05),而Fas和FasL蛋白的表达各组差异均无统计学意义(P>0.05)。结论:DATS-PBCA-NP对肝脏具有明显的靶向性,能显著抑制肝癌体内生长,其机制可能是抑制肿瘤细胞的恶性增殖。

Objective： To study the anti-tumor effect and the relevant mechanism of the hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide （DATS-PBCA-NP） on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice. Methods： The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mouse liver. Then, they were divided into 4 groups： the normal saline （NS） group, the empty nanoparticles group, the diallyl trisulfide （DAIS） group, and the DAIS-PBCA-NP group. Two weeks later, the tumor volume was determined, the PCNA expression in cancer tissues was determined by using immunohistochemistry, and the apoptosis and cell proliferation were determined by Western blot. Results： The success rate of tumor orthotopic transplantation was 100%. Intravenous administration of DATS-PBCA-NP significantly delayed the growth of orthotopic transplantation hepatoma in nude mice （compared with the other three groups, all P 〈0.05）. The results of immunohistochemistry and western blot analysis showed that tumors from DATS-PBCA-NP-treated mice exhibited a markedly down-regulating expression of PCNA compared with the control tumor. There was no significant difference in the expression of Fas and FasL proteins among the four groups （ P 〉0.05）. Conclusion： DATS-PBCA-NP has a significant antitumor effect on the orthotopic transplantation HCC model in association with the suppression of proliferation of tumor cells.