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International Journal of Molecular Medicine
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2014-January Volume 33 Issue 1

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Article

P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11

  • Authors:
    • Wu Luo
    • Yonglin Yu
    • Ruixue Wang
    • Dan He
    • Cong Wang
    • Xiangfeng Zeng
    • Xilei Chen
    • Xiangpeng Tan
    • Tao Huang
    • Xiaoping Wu
  • View Affiliations / Copyright

    Affiliations: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, Guangdong, P.R. China
  • Pages: 194-200
    |
    Published online on: November 4, 2013
       https://doi.org/10.3892/ijmm.2013.1547
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Abstract

The low survival rate of patients with colorectal cancer (CRC) is mainly due to the drug resistance of tumor cells to chemotherapeutic agents. It has been reported that basic fibroblast growth factor (bFGF) is an essential factor involved in the epigenetic mechanisms of drug resistance, which provides a novel potential target for improving the sensitivity of tumor cells to chemotherapeutic agents. In this study, we first demonstrate that a novel bFGF antagonist, peptide P7, previously isolated by phage display technology, reversed bFGF-induced resistance to irinotecan hydrochloride (CPT-11), and counteracted the anti-apoptotic effects of bFGF on CPT-11-treated HT-29 cells. Further experiments indicated that the inhibition of Akt activation, the suppression of bFGF internalization, the increase in the Bax to Bcl-2 ratio and the downregulation of cytokeratin 8 (CK8) by P7 may contribute to the counteracting of the anti-apoptotic effects of bFGF, and further reversal of bFGF-induced resistance to CPT-11. Our results suggest that peptide P7 may have therapeutic potential in CRC as a sensitizer to chemotherapeutic agents by targeting bFGF.
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1 

Kronborg O, Ugstad M, Fuglerud P, Johne B, Hardcastle J, Scholefield JH, Vellacott K, Moshakis V and Reynolds JR: Faecal calprotectin levels in a high risk population for colorectal neoplasia. Gut. 46:795–800. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Lum BL, Fisher GA, Brophy NA, Yahanda AM, Adler KM, Kaubisch S, Halsey J and Sikic BI: Clinical trials of modulation of multidrug resistance. Pharmacokinetic and pharmacodynamic considerations. Cancer. 72(Suppl 11): 3502–3514. 1993. View Article : Google Scholar : PubMed/NCBI

3 

Barrand MA, Bagrij T and Neo SY: Multidrug resistance-associated protein, a protein distinct from P-glycoprotein involved in cytotoxic drug expulsion. Gen Pharmacol. 28:639–645. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Fidler IJ: Critical determinants of cancer metastasis: rationale for therapy. Cancer Chemother Pharmacol. 43:S3–S10. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Broxterman HJ, Lankelma J and Pinedo HM: How to probe clinical tumour samples for P-glycoprotein and multidrug resistance-associated protein. Eur J Cancer. 32A:1024–1033. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Ferry DR, Traunecker H and Kerr DJ: Clinical trials of P-glycoprotein reversal in solid tumours. Eur J Cancer. 32A:1070–1081. 1996. View Article : Google Scholar : PubMed/NCBI

7 

Hertzberg RP, Caranfa MJ and Hecht SM: On the mechanism of topoisomerase I inhibition by camptothecin: evidence for binding to an enzyme-DNA complex. Biochemistry. 28:4629–4638. 1989. View Article : Google Scholar : PubMed/NCBI

8 

Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL and Miller LL: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 343:905–914. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Ichiki M, Gohara R, Rikimaru T, Kitajima T, Fujiki R, Shimada A and Aizawa H: Combination chemotherapy with irinotecan and ifosfamide as second-line treatment of refractory or sensitive relapsed small cell lung cancer: a phase II study. Chemotherapy. 49:200–205. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Takeuchi S, Takamizawa H, Takeda Y, Ohkawa T, Tamaya T, Noda K, Sugawa T, Sekiba K, Yakushiji M and Taguchi T: An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers. Gan To Kagaku Ryoho. 18:579–584. 1991.(In Japanese).

11 

Wall ME: Camptothecin and taxol: discovery to clinic. Med Res Rev. 18:299–314. 1998. View Article : Google Scholar : PubMed/NCBI

12 

Fukuoka M, Niitani H, Suzuki A, Motomiya M, Hasegawa K, Nishiwaki Y, Kuriyama T, Ariyoshi Y, Negoro S and Masuda N: A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. J Clin Oncol. 10:16–20. 1992.PubMed/NCBI

13 

Ohno R, Okada K, Masaoka T, Kuramoto A, Arima T, Yoshida Y, Ariyoshi H, Ichimaru M, Sakai Y and Oguro M: An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. J Clin Oncol. 8:1907–1912. 1990.PubMed/NCBI

14 

Shimada Y, Yoshino M, Wakui A, Nakao I, Futatsuki K, Sakata Y, Kambe M, Taguchi T and Ogawa N: Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group. J Clin Oncol. 11:909–913. 1993.PubMed/NCBI

15 

Shirao K, Shimada Y, Kondo H, Saito D, Yamao T, Ono H, Yokoyama T, Fukuda H, Oka M, Watanabe Y, Ohtsu A, Boku N, Fujii T, Oda Y, Muro K and Yoshida S: Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. J Clin Oncol. 15:921–927. 1997.PubMed/NCBI

16 

Takeuchi S, Dobashi K, Fujimoto S, Tanaka K, Suzuki M, Terashima Y, Hasumi K, Akiya K, Negishi Y and Tamaya T: A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers. Gan To Kagaku Ryoho. 18:1681–1689. 1991.(In Japanese).

17 

Rusnati M and Presta M: Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr Pharm Des. 13:2025–2044. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Cronauer MV, Schulz WA, Seifert HH, Ackermann R and Burchardt M: Fibroblast growth factors and their receptors in urological cancers: basic research and clinical implications. Eur Urol. 43:309–319. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Gross JL, Herblin WF, Dusak BA, Czerniak P, Diamond MD, Sun T, Eidsvoog K, Dexter DL and Yayon A: Effects of modulation of basic fibroblast growth factor on tumor growth in vivo. J Natl Cancer Inst. 85:121–131. 1993. View Article : Google Scholar : PubMed/NCBI

20 

Wu X, Yan Q, Huang Y, Huang H, Su Z, Xiao J, Zeng Y, Wang Y, Nie C, Yang Y and Li X: Isolation of a novel basic FGF-binding peptide with potent antiangiogenetic activity. J Cell Mol Med. 14:351–356. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Wang C, Lin S, Nie Y, Jia X, Wang J, Xiao J, Wu J, Li X and Wu X: Mechanism of antitumor effect of a novel bFGF binding peptide on human colon cancer cells. Cancer Sci. 101:1212–1218. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Bonnet H, Filhol O, Truchet I, Brethenou P, Cochet C, Amalric F and Bouche G: Fibroblast growth factor-2 binds to the regulatory beta subunit of CK2 and directly stimulates CK2 activity toward nucleolin. J Biol Chem. 271:24781–24787. 1996. View Article : Google Scholar : PubMed/NCBI

23 

Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI

24 

Sorensen V, Nilsen T and Wiedlocha A: Functional diversity of FGF-2 isoforms by intracellular sorting. Bioessays. 28:504–514. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Gan Y, Wientjes MG and Au JL: Expression of basic fibroblast growth factor correlates with resistance to paclitaxel in human patient tumors. Pharm Res. 23:1324–1331. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Walsh CT, Wei Y, Wientjes MG and Au JL: Quantitative image analysis of intra-tumoral bFGF level as a molecular marker of paclitaxel resistance. J Transl Med. 6:42008. View Article : Google Scholar : PubMed/NCBI

27 

Wang Q, Maloof P, Wang H, Fenig E, Stein D, Nichols G, Denny TN, Yahalom J and Wieder R: Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Exp Cell Res. 238:177–187. 1998. View Article : Google Scholar : PubMed/NCBI

28 

Burchill SA and Westwood G: Mechanism of basic fibroblast growth factor-induced cell death. Apoptosis. 7:5–12. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Coleman AB: Positive and negative regulation of cellular sensitivity to anti-cancer drugs by FGF-2. Drug Resist Updat. 6:85–94. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Maloof P, Wang Q, Wang H, Stein D, Denny TN, Yahalom J, Fenig E and Wieder R: Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat. 56:153–167. 1999. View Article : Google Scholar : PubMed/NCBI

31 

Raisova M, Hossini AM, Eberle J, Riebeling C, Wieder T, Sturm I, Daniel PT, Orfanos CE and Geilen CC: The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol. 117:333–340. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Wang Y, He QY, Tsao SW, Cheung YH, Wong A and Chiu JF: Cytokeratin 8 silencing in human nasopharyngeal carcinoma cells leads to cisplatin sensitization. Cancer Lett. 265:188–196. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Jaquemar D, Kupriyanov S, Wankell M, Avis J, Benirschke K, Baribault H and Oshima RG: Keratin 8 protection of placental barrier function. J Cell Biol. 161:749–756. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Caulin C, Ware CF, Magin TM and Oshima RG: Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. J Cell Biol. 149:17–22. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Gilbert S, Loranger A, Daigle N and Marceau N: Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. J Cell Biol. 154:763–773. 2001. View Article : Google Scholar

36 

Fortier AM, Van Themsche C, Asselin E and Cadrin M: Akt isoforms regulate intermediate filament protein levels in epithelial carcinoma cells. FEBS Lett. 584:984–988. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Wang C, Yu Y, Li Q, et al: P7 peptides suppress the proliferation of K562 cells induced by basic fibroblast growth factor. Tumour Biol. 33:1085–1093. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Yu Y, Gao S, Li Q, et al: The FGF2-binding peptide P7 inhibits melanoma growth in vitro and in vivo. J Cancer Res Clin Oncol. 138:1321–1328. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Luo W, Yu Y, Wang R, He D, Wang C, Zeng X, Chen X, Tan X, Huang T, Wu X, Wu X, et al: P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11. Int J Mol Med 33: 194-200, 2014.
APA
Luo, W., Yu, Y., Wang, R., He, D., Wang, C., Zeng, X. ... Wu, X. (2014). P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11. International Journal of Molecular Medicine, 33, 194-200. https://doi.org/10.3892/ijmm.2013.1547
MLA
Luo, W., Yu, Y., Wang, R., He, D., Wang, C., Zeng, X., Chen, X., Tan, X., Huang, T., Wu, X."P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11". International Journal of Molecular Medicine 33.1 (2014): 194-200.
Chicago
Luo, W., Yu, Y., Wang, R., He, D., Wang, C., Zeng, X., Chen, X., Tan, X., Huang, T., Wu, X."P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11". International Journal of Molecular Medicine 33, no. 1 (2014): 194-200. https://doi.org/10.3892/ijmm.2013.1547
Copy and paste a formatted citation
x
Spandidos Publications style
Luo W, Yu Y, Wang R, He D, Wang C, Zeng X, Chen X, Tan X, Huang T, Wu X, Wu X, et al: P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11. Int J Mol Med 33: 194-200, 2014.
APA
Luo, W., Yu, Y., Wang, R., He, D., Wang, C., Zeng, X. ... Wu, X. (2014). P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11. International Journal of Molecular Medicine, 33, 194-200. https://doi.org/10.3892/ijmm.2013.1547
MLA
Luo, W., Yu, Y., Wang, R., He, D., Wang, C., Zeng, X., Chen, X., Tan, X., Huang, T., Wu, X."P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11". International Journal of Molecular Medicine 33.1 (2014): 194-200.
Chicago
Luo, W., Yu, Y., Wang, R., He, D., Wang, C., Zeng, X., Chen, X., Tan, X., Huang, T., Wu, X."P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11". International Journal of Molecular Medicine 33, no. 1 (2014): 194-200. https://doi.org/10.3892/ijmm.2013.1547
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