Antitumor effect of FP3 in a breast cancer xenograft model

Lan,Huanrong; Zheng,Lingzhi; Jin,Ketao; Teng,Lisong

doi:10.3892/etm.2012.773

Antitumor effect of FP3 in a breast cancer xenograft model

Authors:
- Huanrong Lan
- Lingzhi Zheng
- Ketao Jin
- Lisong Teng
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Affiliations: Department of Plastic Surgery, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, P.R. China, Department of Gynecology and Obstetrics, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, P.R. China, Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, P.R. China, Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: October 26, 2012 https://doi.org/10.3892/etm.2012.773
Pages: 85-88

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Abstract

FP3 is a novel vascular endothelial growth factor (VEGF) blocker proposed to have antiangiogenic properties. Previous studies revealed that FP3 is a new promising agent for treating human choroidal neovascularization (CNV)‑associated age‑associated macular degeneration (AMD) and has an inhibitory effect on VEGF‑mediated proliferation and migration of human umbilical vein endothelial cells and VEGF‑mediated vessel sprouting of the rat aortic ring in vitro. Previous studies have also revealed that FP3 has antitumor effects and antiangiogenic effects in a non‑small cell lung cancer cell line (A549), as well as in patient‑derived tumor tissue xenograft models of gastric cancer and colon carcinoma with lymphatic and hepatic metastases in nude mice. In the present study, the antitumor effect of FP3 in an MDA‑MB‑231 breast cancer xenograft model was investigated. Treatment with FP3 for 3 weeks significantly suppressed xenograft growth and this inhibition was associated with a significant decrease in angiogenesis and direct inhibition of tumor cells. The results of the present study indicate that FP3 inhibits breast cancer tumor growth via the indirect inhibition of angiogenesis as well as a direct effect on tumor cells.

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1	Folkman J: Fundamental concepts of the angiogenic process. Curr Mol Med. 3:643–651. 2003. View Article : Google Scholar : PubMed/NCBI
2	Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar : PubMed/NCBI
3	Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI
4	Ferrara N: Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 25:581–611. 2004. View Article : Google Scholar : PubMed/NCBI
5	Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS and Dvorak HF: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 219:983–985. 1983. View Article : Google Scholar
6	Shibuya M: Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct. 26:25–35. 2001. View Article : Google Scholar : PubMed/NCBI
7	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
8	Cook KM and Figg WD: Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin. 60:222–243. 2010. View Article : Google Scholar : PubMed/NCBI
9	Brown LF, Berse B, Jackman RW, Tognazzi K, Guidi AJ, Dvorak HF, Senger DR, Connolly JL and Schnitt SJ: Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol. 26:86–91. 1995. View Article : Google Scholar : PubMed/NCBI
10	Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B and Henriksson R: Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. J Clin Oncol. 18:1423–1431. 2000.
11	Teng LS, Jin KT, He KF, Wang HH, Cao J and Yu DC: Advances in combination of antiangiogenic agents targeting VEGF-binding and conventional chemotherapy and radiation for cancer treatment. J Chin Med Assoc. 73:281–288. 2010. View Article : Google Scholar : PubMed/NCBI
12	Teng LS, Jin KT, He KF, Zhang J, Wang HH and Cao J: Clinical applications of VEGF-trap (aflibercept) in cancer treatment. J Chin Med Assoc. 73:449–456. 2010. View Article : Google Scholar : PubMed/NCBI
13	Jin K, He K, Teng F, Li G, Wang H, Han N, Xu Z, Cao J, Wu J, Yu D and Teng L: FP3: a novel VEGF blocker with antiangiogenic effects in vitro and antitumour effects in vivo. Clin Transl Oncol. 13:878–884. 2011. View Article : Google Scholar : PubMed/NCBI
14	Zhang M, Zhang J, Yan M, Li H, Yang C and Yu D: Recombinant anti-vascular endothelial growth factor fusion protein efficiently suppresses choridal neovascularization in monkeys. Mol Vis. 14:37–49. 2008.
15	Zhang M, Yu D, Yang C, Xia Q, Li W, Liu B and Li H: The pharmacology study of a new recombinant human VEGF receptor-fc fusion protein on experimental choroidal neovascularization. Pharm Res. 26:204–210. 2009. View Article : Google Scholar : PubMed/NCBI
16	Zhang M, Zhang J, Yan M, Luo D, Zhu W, Kaiser PK and Yu DC; KH902 Phase 1 Study Group: A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration. Ophthalmology. 118:672–678. 2011. View Article : Google Scholar : PubMed/NCBI
17	Jin K, He K, Han N, Li G, Wang H, Xu Z, Jiang H, Zhang J and Teng L: Establishment of a PDTT xenograft model of gastric carcinoma and its application in personalized therapeutic regimen selection. Hepatogastroenterology. 58:1814–1822. 2011.PubMed/NCBI
18	Jin K, Li G, Cui B, Zhang J, Lan H, Han N, Xie B, Cao F, He K, Wang H, Xu Z, Teng L and Zhu T: Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases. PLoS One. 6:e283842011. View Article : Google Scholar : PubMed/NCBI
19	Huang J, Frischer JS, New T, Kim ES, Serur A, Lee A, Kadenhe-Chiwishe A, Pollyea DA, Yokoi A, Holash J, Yancopoulos GD, Kandel JJ and Yamashiro DJ: TNP-470 promotes initial vascular sprouting in xenograft tumors. Mol Cancer Ther. 3:335–343. 2004.PubMed/NCBI
20	Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD and Rudge JS: VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 99:11393–11398. 2002. View Article : Google Scholar : PubMed/NCBI
21	Roskoski R Jr: Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 62:179–213. 2007. View Article : Google Scholar : PubMed/NCBI
22	Borgström P, Gold DP, Hillan KJ and Ferrara N: Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res. 19:4203–4214. 1999.PubMed/NCBI