title: Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer.
abstract: Insulin-like growth factors are known to inhibit apoptosis and promote tumour angiogenesis. Previously we have shown that insulin-like growth factor binding protein-4 (IGFBP-4) gene therapy increased apoptosis and decreased mitosis in colon cancer. In this experiment we used HT-29 colon cancer cells to induce subcutaneous cancers in nude mice and administered either the mammalian expression vector with IGFBP-4 insert or vector only around the tumour site. Three weeks after gene transfer, tumours were harvested and expressions of Bax, Bcl-2 and IGF-I receptor in tumours were determined by Western blotting and immunofluorescence. Micro-vessel counting was performed by immunostaining with CD34 and von Willebrand antibodies. Results showed that tumours treated with IGFBP-4 gene had higher expression of Bax, lower expression of Bcl-2 and IGF-I receptor. Bcl-2 was localised to tumour cell cytoplasm while Bax was expressed both in the interstitial area and cytoplasm. IGFBP-4 treatment also decreased micro-vessel count in tumour tissues. Micro-vessels were mainly located in the periphery and interstitial area. This experiment shows that IGFBP-4 gene therapy increases tumour apoptosis via altering the expressions of Bcl-2 and Bax and decreasing the angiogenesis in colorectal cancer.
authors.affiliation: Academic Division of Surgical and Interventional Sciences, University College London, Hampstead Campus, and Royal Free Hampstead NHS Trust Hospital, London NW3 2FP, UK.
authors.forename: Rajaraman
authors.initials: R
authors.lastname: Durai
authors.forename: Shi Yu
authors.initials: SY
authors.lastname: Yang
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Sales
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Goldspink
authors.forename: Marc C
authors.initials: MC
authors.lastname: Winslet
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000628:therapy*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein