Yin Jian-Hua, Zhu Xiao-Yan, Shi Wei-Dong, Liu Lu-Ming
Department of Integrative Oncology, Cancer Hospital, Fudan University, 270 Dong An Road, Shanghai 200032, China.
BMC Complement Altern Med. 2014 Dec 13;14:483. doi: 10.1186/1472-6882-14-483.
Huachansu injection (HCS) is a water-soluble preparation made from Bufo gargarizans's skin, which has been widely used in clinics for tumor therapy in China. Though the anti-cancer activity of HCS has been verified through studies in vitro and in vivo, there is little research about its potential anti-metastasis effect. The primary objective of this study was to assess the effects of HCS on both the invasion of pancreatic cancer cells in vitro and on the progression of liver metastasis in vivo in this study.
HCS anti-metastasis potential was accessed using both assay of Cell viability and invasion in vitro, and then further Establishing xenograft model in nude mice. In the cell-based assay, mRNA and protein expression of MMP-2, MMP-9 and VEGF was detected by semi-quantitative RT-PCR and western blotting. In animal experiment, liver metastasis nodules and change of liver-body ratio was observed. Meanwhile, correlation of the CA19-9 and CEA content in serum with the progression of liver metastasis was analyzed.
We observed that HCS prevented the invasion of cancer cells, with inhibiting the expressions of MMP-2 and MMP-9, and reduced not only the number of metastasis nodules but the ratio of liver-body weight as well. Furthermore, HCS decreased the expression of MMP-2, MMP-9 and VEGF in liver metastasis, while also reducing CA19-9 contents in serum. In addition, correlation analysis indicated that the level of CA19-9 in serum was closely related to the number of liver metastasis nodules.
Our experimental results suggest that HCS has some anti-metastasis potential to suppress the growth of liver metastasis by decreasing the expression of MMP-2 and MMP-9 as well as VEGF.
华蟾素注射液(HCS)是一种由中华大蟾蜍皮肤制成的水溶性制剂,在中国已广泛应用于临床肿瘤治疗。尽管HCS的抗癌活性已在体外和体内研究中得到验证,但其潜在的抗转移作用的研究却很少。本研究的主要目的是评估HCS对体外胰腺癌细胞侵袭和体内肝转移进展的影响。
通过体外细胞活力和侵袭试验评估HCS的抗转移潜力,然后进一步建立裸鼠异种移植模型。在细胞试验中,通过半定量RT-PCR和蛋白质印迹法检测基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和血管内皮生长因子(VEGF)的mRNA和蛋白表达。在动物实验中,观察肝转移结节和肝体比的变化。同时,分析血清中CA19-9和癌胚抗原(CEA)含量与肝转移进展的相关性。
我们观察到HCS可抑制癌细胞侵袭,抑制MMP-2和MMP-9的表达,不仅减少转移结节的数量,还降低肝体重比。此外,HCS降低肝转移中MMP-2、MMP-9和VEGF的表达,同时也降低血清中CA19-9的含量。此外,相关性分析表明血清中CA19-9水平与肝转移结节数量密切相关。
我们的实验结果表明,HCS具有一定的抗转移潜力,可通过降低MMP-2、MMP-9和VEGF的表达来抑制肝转移的生长。