Inhibitory Effects Of Recombinant Adenovirus-mediated Overexpression Of TIMP-1 On Invasion And Metastasis Of Hepatocellular Carcinoma

Objective Human hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide, because it's generally highly proliferative, invasive, and metastatic. HCC frequently shows early invasion into blood vessels as well as intrahepatic metastases and later shows extrahepatic metastases. Matrix metalloproteinases (MMPs) and its natural tissue inhibitors (TIMPs) are involved in cancer progression. This study was undertaken to determine the effects of overexpression of TIMP-1 on human HCC cells growth, proliferation, invasion and metastasis. Methods Employing the efficient AdEasy? system, the recombinant adenovirus AdTIMP-1 containing full-length cDNA of TIMP-1 was generated by homologous recombination and amplified in HEK293 cells. HepG2 cells were then transfected by AdhTIMP-1 (MOI 100) and a series of experiments was performed. The mRNA and protein expressions of TIMP-1 were detected with RT-PCR and Western blotting, respectively. The ultrastructure was observed by transmission electron microscope (TEM) and the proliferation was determined by MTT assay and growth curve. The potential of in-vitro invasion was measured using Millicell Chamber. In the in-vivo experiment, the nude mice were injected with HepG2 cells to establish tumor models and then intratumoral injection of AdTIMP-1 into...