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Pharmaceutical Research

, Volume 23, Issue 6, pp 1324–1331 | Cite as

Expression of Basic Fibroblast Growth Factor Correlates with Resistance to Paclitaxel in Human Patient Tumors

  • Yuebo Gan
  • M. Guillaume Wientjes
  • Jessie L.-S. AuEmail author
Research Paper

Background

Preclinical results indicate acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) present in solid tumors as a cause of broad-spectrum chemoresistance, whereas earlier clinical studies suggest that bFGF expression is associated with opposing outcomes in patients. We investigated the relationship between FGF expression and paclitaxel activity in tumors from bladder, breast, head and neck, ovarian, and prostate cancer patients.

Materials and Methods

Tumors (n = 96) were maintained in three-dimensional histocultures, retaining tumor–stromal interaction. Bladder tumors were treated with paclitaxel for 2 h, and the other tumors for 24 h. Antiproliferative and proapoptotic effects of paclitaxel were quantified and correlated with expression of aFGF, bFGF, P-glycoprotein (Pgp), p53, and bcl-2.

Results

Fifty-one percent (49/96) and 63% (61/96) of tumors showed aFGF and bFGF staining, respectively. aFGF expression was positively correlated with tumor stage (p < 0.01), and bFGF expression with tumor grade and Pgp expression (p < 0.05). Paclitaxel inhibited antiproliferation in 86% of tumors (83/96), with an average inhibition of 46 ± 19% (mean ± SD) in the responding tumors. Paclitaxel also induced apoptosis in 96% of tumors (92/96), with an average apoptotic index of 12 ± 7% in the responding tumors. aFGF expression did not correlate with tumor sensitivity to paclitaxel, whereas bFGF expression showed an inverse correlation (p < 0.01). bFGF expression was a stronger predictor of paclitaxel resistance compared to Pgp, p53, or Bcl-2.

Conclusion

These results support a role of bFGF in paclitaxel resistance in human patient tumors.

Key Words

fibroblast growth factor paclitaxel resistance 

Notes

Aknowledgments

This study was supported in part by a research grant R01CA97067 from the National Cancer Institute, NIH, DHHS. The excellent technical support of Jie Lu is gratefully acknowledged.

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Yuebo Gan
    • 1
  • M. Guillaume Wientjes
    • 1
    • 2
  • Jessie L.-S. Au
    • 1
    • 2
    Email author
  1. 1.College of PharmacyThe Ohio State UniversityColumbusUSA
  2. 2.James Cancer Hospital and Solove Research InstituteThe Ohio State UniversityColumbusUSA

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