Abstract
Gastric cancer is the second cause of the common cancer deaths worldwide. Basic fibroblast growth factor (bFGF) was up-regulated in patients with gastric cancer and was regarded as a potential therapeutic target. We have previously obtained a high-affinity bFGF-binding peptide (named P7) from the phage display random heptapeptide library. In this study, we first proved that P7 peptides inhibited proliferation of gastric cancer cell lines including SGC-7901, AGS, and BGC-823 cells stimulated with bFGF. Further investigations with SGC-7901 cells revealed that the mechanisms of P7 peptides inhibiting bFGF-stimulated cell proliferation in vitro involved cell cycle arrest at the G0/G1 phase, blockade of the activation of Erk and P38 cascades, and suppression of bFGF internalization. The results suggested that the bFGF-binding peptide may have therapeutic potential in gastric cancer therapy.
Similar content being viewed by others
References
Bailly K, Soulet F, Leroy D, Amalric F, Bouche G (2000) Uncoupling of cell proliferation and differentiation activities of basic fibroblast growth factor. FASEB J 14(2):333–344
Cronauer MV, Schulz WA, Seifert HH, Ackermann R, Burchardt M (2003) Fibroblast growth factors and their receptors in urological cancers: basic research and clinical implications. Eur Urol 43(3):309–319. doi:10.1016/s0302-2838(03)00005-8
Dailey L, Ambrosetti D, Mansukhani A, Basilico C (2005) Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev 16(2):233–247. doi:10.1016/j.cytogfr.2005.01.007
Gross JL, Herblin WF, Dusak BA, Czerniak P, Diamond MD, Sun T, Eidsvoog K, Dexter DL, Yayon A (1993) Effects of modulation of basic fibroblast growth factor on tumor growth in vivo. J Natl Cancer Inst 85(2):121–131. doi:10.1093/jnci/85.2.121
Neary JT, Kang Y, Shi Y-F (2005) Cell cycle regulation of astrocytes by extracellular nucleotides and fibroblast growth factor-2. Purinergic Signal 1(4):329–336. doi:10.1007/s11302-005-8075-y
Peng L, Ran Y-L, Hu H, Yu L, Liu Q, Zhou Z, Sun Y-M, Sun L-C, Pan J, Sun L-X, Zhao P, Yang Z-H (2009) Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Src/FAK pathway. Carcinogenesis 30(10):1660–1669. doi:10.1093/carcin/bgp178
Rusnati M, Presta M (2007) Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr Pharm Des 13(20):2025–2044
Sorensen V, Nilsen T, Wiedlocha A (2006) Functional diversity of FGF-2 isoforms by intracellular sorting. Bioessays 28(5):504–514. doi:10.1002/bies.20405
Tsujimoto H, Ono S, Ichikura T, Matsumoto Y, Yamamoto J, Hase K (2010) Roles of inflammatory cytokines in the progression of gastric cancer: friends or foes? Gastric Cancer 13(4):212–221. doi:10.1007/s10120-010-0568-x
Wang C, Lin S, Nie Y, Jia X, Wang J, Xiao J, Wu J, Li X, Wu X (2010) Mechanism of antitumor effect of a novel bFGF binding peptide on human colon cancer cells. Cancer Sci 101(5):1212–1218. doi:10.1111/j.1349-7006.2010.01501.x
Wu X, Yan Q, Huang Y, Huang H, Su Z, Xiao J, Zeng Y, Wang Y, Nie C, Yang Y, Li X (2010) Isolation of a novel basic FGF-binding peptide with potent antiangiogenetic activity. J Cell Mol Med 14(1–2):351–356. doi:10.1111/j.1582-4934.2008.00506.x
Wu X, Jia X, Ji Y, Wang C, Yu Y, Gao S, Li Q, Li X (2011) Effects of a synthetic bFGF antagonist peptide on the proteome of 3T3 cells stimulated with bFGF. Int J Pept Res Ther 17. doi:10.1007/s10989-011-9240-5
Zhang W, Chu Y-Q, Ye Z-Y, Zhao Z-S, Tao H-Q (2009) Expression of hepatocyte growth factor and basic fibroblast growth factor as prognostic indicators in gastric cancer. Anat Rec Adv Integr Anat Evol Biol 292(8):1114–1121. doi:10.1002/ar.20934
Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (30973671, 81071800), the Natural Science Foundation of Zhejiang Province of China (Y2090292), the Natural Science Foundation of Guangdong Province of China (9151064001000031), the Science and Technology Planning Project of Wenzhou (Y20090244), the Fundamental Research Funds for the Central Universities (X. P. Wu), Guangdong Provincial “Thousand-Hundred-Ten Talent Project” (X. P. Wu), and Guangdong Provincial Key Discipline in Biochemistry and Molecular biology.
Author information
Authors and Affiliations
Corresponding author
Additional information
S. Gao and Y. Yu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Gao, S., Yu, Y., Lai, X. et al. Anti-Proliferation Effect of a Short Peptide on bFGF-Induced Human Gastric Cancer Cells. Int J Pept Res Ther 18, 299–304 (2012). https://doi.org/10.1007/s10989-012-9301-4
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10989-012-9301-4