Influence Of △Np73 Expression On Invasive Properties Of Human Colorectal Cancer And The Effect Of Antisense △Np73 As Gene-therapy For Human Colorectal Cancer

Background: Human colorectal cancer is extramely harmful to the life and health of human beings. Its genesis is related to multiple factors. It has been proved that there is approximately 46% in human colorectal cancer with gene mutation.ΔNp73 gene is a homologue of p73.ΔNp73 gene is a kind of short armed p73 which lacks the transcriptional activation domain. Many studies show thatΔNp73 gene is clearly involved in cancer, but it shows contradictory effect in different cancers such as the virtual absence of inacticating mutaions, tumor-associated over expression ofΔNp73 in many different human cancers, and lack of phenotype inΔNp73-nude mice are in consistent with a classic suppressor function. How to explain the paradoxical behave ofΔNp73 gene? It has been proved thatΔNp73 gene was overexpression in human colorectal cancer and nearly hans't mutation. But the effect ofΔNp73 on invasion in human colorectal cancer is still unknown.Objective To investigate the relationship between the expression ofΔNp73 and the invasiveness of human colorectal cancer, explore the effects of antisenseΔNp73 gene on growth and metastasis in cells of human colorectal cancer and to evaluate its potential use in anti-angiogenesis. Then find a new way for human colorectal cancer gene therapy.Methods: This study use LOVO cell,a kind cell of human colorectal cancer.ΔNp73 was transferred into LOVO cell by liposome, and the positive cell clones were chosen by G418. The effect ofΔNp73 gene on cell growth was detected by trypan blue counter measurement, cell growth curve and flow cytometry. Western-blot were employed to detect the expression of VEGF. And then, AS-ΔNp73 was transferred into LOVO by liposome. Growth curve and expression of VEGF protein were detected in the same way. LOVO-ΔNp73 and AS-ΔNp73 were transplanted into nude mice. The MVD and immunohistochemical staining were detecterd in the transplanted tumor.Results Erexpression ofΔNp73 gene cell clones were chosen successfully. The growth of LOVO-ΔNp73 cells were significantly increased。The expression of VEGF in theΔNp73-LOVO was significantly higher than control group (p<0.01). The VEGF protein expression in LOVO cell increased afterΔNp73 gene was transfered into LOVO cell (P<0.01).ΔNp73 promoted the growth of tumor transplanted in nude mice and increased the tumor MVD (p<0.05). The growth of LOVO-ASΔNp73 cells was significantly decreased. The invasive cell number was significantly decreased in LOVO-ASΔNp73 cells than in LOVO-ΔNp73 (P<0.01). The VEGF mRNA expression was dramatically decreased after transfection of antisenseΔNp73. The MVD of tumor in nude mice was decreased after transfection of antisenseΔNp73 (P<0.01).ConclusionsΔNp73 play an important role in zhe invasiveness of human colorectal cancer. Overexpression ofΔNp73 facilitates human colorectal cancer. It can be defined as an oncogene. AntisenseΔNp73 inhibited the growth of cells of colorectal cancer and suppressed angiogenesis in tumor. AntisenseΔNp73 may provide a new therapeutic approach in gene therapy for human colorectal cancer.