| Colorectal carcinoma is the second common malignant tumor in digestive tract. The main reason for its treatment failure is the development of hematogenous metastasis and lymphatic metastasis. It is shown that both the invasive capability of cancerous cells and the neogenesis of blood vessels and lympgatic vessels are closely related with the metastasis of colorectal carcinoma. And the density of blood vessels and lympgatic vessels is correctly related with lymphatic metastasis and the prognosis of colorectal cancer. Inhibiting the neogenesis of blood vessels can decrease the blood supply of the tumor, induce the apoptosis of cancerous cells and reduce the incidence of metastasis. The effective treatment target, especially endostatin, for colorectal cancer has been widely studied.Endostatin is a specific inhibitor of vessel endothelium. On the cellular level, it has been reported that endostatin inhibited endothelial cell proliferation and migration, and induced endothelial cell apoptosis and cell cycle arrest. Some animal experiments have confirmed that endostatin could inhibit tumor growth through anti-angiogenesis and resulted in the decrease of invasion and metastasis of cancer, and it would not easily induced drug resistance in the cells. Recently reports found that the endostatin could inhibit the invasion of some tumor cells, such as the human tongue carcinoma cell, the head and neck squamous cell carcinoma cells, the uterine cervix cancer cell Hela, the laryngeal carcinoma cells(Hep-2), and so on. However, it is short of systematic study of the role of endostatin in the colorectal carcinoma. Moreover, angiogenesis and lymphangiogenesis are directly related with the infiltration and metastasis of carcinoma. The angiogenesis and lymphangiogenesis is a process of proliferation, migration and canaliculization of the endothelial cells. However, the role of endostatin in the the neogenesis of lympgatic vessels it is still unclear.Vascular endothelial growth factor(VEGF)-A have been identified as one of the specific angiogenesis factors, while vascular endothelial growth factor (VEGF)-C and -D play important roles in lymphangiogenesis and metastasis. It has been proved that endostatin can exert antiangiogenic effect via blocking VEGF or bFGF-induced the migration of endothelial cells, but whether it adjust the expressions of VEGF family of colorectal carcinoma, has not been systematically studied.HGF, also known as scatter factor (SF), it is a growth factor with pleiotropic effects including mitogen, mobility factor and morphogen and so on. HGF's activities are mediated by a membrane-spanning receptor tyrosine kinase, the HGF receptor (HGF-R, also known as MET/c-met). It has been proved that HGF plays an important role in the infiltration and metastasis of cancerous cells and the neogenesis of blood vessels. Recently, many studies indicated that HGF may be an enhancing factor in the neogenesis of lymphatic vessels. Therefore, it is necessary to find out the role of endostatin in the expression of HGF and c-Met of colorectal carcinoma.This experiment used a combinative method of formation and function to examine the effects of endostatin on the proliferation and migration of SW620 and the influence of endostatin on the expression of VEGF-A, VEGF-C,VEGF-D,HGF and c-Met in SW620, systematically.Methods:1 MTT was used to analyse the effect of endostatin on the proliferation.2 The effect of endostatin on the cell cycle was determined by FCM.3 The effect of endostatin on the migration of cells was studied by restoration of basal membrane.4 The expressions of VEGF-A, VEGF-C,VEGF-D,HGF and c-Met were determined by Western blotting.Results:1 The results showed that endostatin could inhibit the proliferation of SW620. The effect of endostatin on the proliferation of SW620 increased the concentration of endostatin, but rather slowly. Maximum inhibition of SW620 proliferation by endostatin was only 36.75% at 20ug/ml. 2 The results of FCM showed that endostatin could effect the cell cycle of SW620 but in a feeble way. The cells of endostatin group in G0 /G1 phase were increased by 1.5%, the cells in G2/M phase decreased by 2.3% compared with the control group. The cells in S phase were increased by 0.9%. The proliferation index of SW620 decreased compared with that of the control group (52.3% vs 53.7%), and the apoptosis rate of SW620 increased littly compared with that of control group (0.57% vs 0.34%).3 Endostatin could inhibit the migration of SW620 in a concentration- dependent manner.4 Endostatin can suppress the expressions of VEGF-A, VEGF-C,VEGF-D,HGF and c-Met of SW620 .Conclusion:Endostatin can inhibit the proliferation and migration of SW620 both in a concentration-dependent way. Endostatin suppress the expressions of VEGF-A, VEGF-C,VEGF-D,HGF and c-Met of SW620.
|
PDF Full Text Request