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Investigators at Huazhong University of Science and Technology Describe Findings in Cancer Gene Therapy

February 3, 2014

By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Fresh data on Biotechnology are presented in a new report. According to news reporting from Wuhan, People's Republic of China, by NewsRx journalists, research stated, "Mouse double minute 2 (MDM2) is overexpressed in many malignant tumors, and MDM2 levels are associated with poor prognosis of several human cancers, including breast cancer. In the present study, we investigated the function of MDM2 in vascular endothelial growth factor (VEGF)-mediated tumor angiogenesis of breast cancer and the potential value of MDM2 as an anti-angiogenic therapy target for cancer therapy by inhibiting MDM2 with antisense oligonucleotides (ASO) or other antagonist nutlin-3."

The news correspondents obtained a quote from the research from the Huazhong University of Science and Technology, "Anti-MDM2 ASO and nutlin-3 were evaluated for their in vitro and in vivo anti-angiogenesis activities in different human breast cancer models with a different p53 status: MCF-7 cell line containing wild-type p53 and MDA-MB-468 cell line containing mutant p53. MCF-7 and MDA-MB-468 cells were incubated with different concentrations of ASO or nutlin-3 for various periods of time. VEGF gene and protein expression in tumor cells was measured by qPCR and Western blot. The level of VEGF protein secreted in the culture supernatant of treated cells was quantified by enzyme-linked immunosorbent assay (ELISA). Nude mouse xenograft models were further established to determine their effects on tumor growth and angiogenesis. Serum levels of VEGF were measured by ELISA. VEGF expression and microvessel density in tumor tissues were studied by immunohistochemistry. Both angiogenesis and tumor growth were digitally quantified. In both MCF-7 and MDA-MB-468 cells, VEGF expression and secretion were reduced, resulting from specific inhibition of MDM2 expression by ASO. In vivo assay, after administration of ASO, VEGF production reduced and anti-angiogenesis activity occurred in nude mice bearing MCF-7 or MDA-MB-468 xenograft. However, in both models treated with nutlin-3, VEGF production was not changed and anti-angiogenesis activity was not observed. In summary, the ASO construct targeting MDM2 specifically suppresses VEGF expression in vitro and VEGF-mediated tumor angiogenesis in vivo in breast cancer."

According to the news reporters, the research concluded: "Furthermore, the suppression of VEGF expression subsequent to inhibition of MDM2 in p53 mutant cells suggests that MDM2 has a regulatory role on VEGF expression through a p53-independent mechanism."

For more information on this research see: Effects of MDM2 inhibitors on vascular endothelial growth factor-mediated tumor angiogenesis in human breast cancer. Angiogenesis, 2014;17(1):37-50. Angiogenesis can be contacted at: Springer, Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands. (Springer -; Angiogenesis -

Our news journalists report that additional information may be obtained by contacting J. Xiong, Huazhong University of Science & Technology, Tongji Med College, Tongji Hosp, Inst Pathol, Wuhan 430030, People's Republic of China. Additional authors for this research include Q. Yang, J.S. Li and S. Zhou (see also Biotechnology).

Keywords for this news article include: Asia, VEGF, Biotechnology, Wuhan, Genetics, Oncology, p53 Gene, Angiogenesis, Breast Cancer, Women's Health, Protein Kinases, Membrane Proteins, Angiogenic Proteins, Cancer Gene Therapy, Phosphotransferases, Growth Factor Receptors, People's Republic of China, Receptor Protein-Tyrosine Kinases

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Source: Cancer Gene Therapy Week

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