Objective: Portal vein metastasis of hepatocellular carcinoma(HCC) results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus(PVTT) is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.Methods: Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits. Results: Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis(P<0.01), significantly enhanced cell metastasis and invasion(P<0.01), whereas cell proliferation and the stages of the cell cycle did not differ significantly(P>0.05). A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum(P<0.05), while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly(P>0.05). Conclusions: Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metastasis and invasion. This effect may be related to
The effect of portal vein tumor thrombus(PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: "hepatocellular carcinoma" AND "portal vein tumor thrombus." Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy(RT), transhepatic arterial chemoembolization(TACE), transarterial radioembolization(TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT,TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.
