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Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 2, pp 249–255 | Cite as

Differential regulation of bladder cancer growth by various glucocorticoids: corticosterone and prednisone inhibit cell invasion without promoting cell proliferation or reducing cisplatin cytotoxicity

  • Hitoshi Ishiguro
  • Takashi Kawahara
  • Yichun Zheng
  • Eiji Kashiwagi
  • Yi Li
  • Hiroshi Miyamoto
Original Article

Abstract

Purpose

A synthetic glucocorticoid, dexamethasone, was recently shown to inhibit bladder cancer cell invasion and metastasis through the glucocorticoid receptor (GR) pathway but increased cell proliferation via inhibiting apoptosis particularly induced by cisplatin. Therefore, comedication with dexamethasone in bladder cancer patients may lead to unfavorable outcomes such as chemoresistance. We here look for any glucocorticoids with inhibitory effects on tumor cell invasion yet inhibitory or at least no stimulatory effects on cell viability.

Methods

The effects of 10 glucocorticoids on cell viability were first assessed in three bladder cancer lines. Selected compounds were further assessed for their ability in cell viability and apoptosis, with or without cisplatin, as well as in cell invasion.

Results

Most of the compounds (hydrocortisone, betamethasone, flumethasone, triamcinolone, budesonide, fluticasone propionate, and fludrocortisone acetate) increased GR-positive cell growth, which was similar to or even stronger than the effect of dexamethasone. Nonetheless, two glucocorticoids (corticosterone, prednisone) showed only marginal effects on cell growth of all the lines tested. They did not significantly reduce the effects of cisplatin on cell proliferation or cisplatin-induced apoptosis. Conversely, corticosterone, prednisone, and dexamethasone similarly inhibited cell invasion and expression of related genes, including MMP-9, VEGF, and IL-6, in GR-positive lines.

Conclusion

Corticosterone and prednisone are suggested to have the potential of being harmless, in contrast to dexamethasone, without promoting cell proliferation or inhibiting cytotoxic activity of cisplatin, yet beneficial to bladder cancer patients via suppressing tumor invasion. Our results are thus useful in improving chemotherapy regimens, including optimal glucocorticoids, for urothelial carcinoma.

Keywords

Bladder cancer Chemotherapy Cisplatin Comedication Glucocorticoids 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hitoshi Ishiguro
    • 1
    • 2
  • Takashi Kawahara
    • 1
    • 2
  • Yichun Zheng
    • 1
    • 2
    • 3
  • Eiji Kashiwagi
    • 1
  • Yi Li
    • 2
    • 3
  • Hiroshi Miyamoto
    • 1
    • 2
    • 4
  1. 1.Departments of Pathology and UrologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Rochester Medical CenterRochesterUSA
  3. 3.Department of Urology, 2nd Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  4. 4.The James Buchanan Brady Urological InstituteThe Johns Hopkins HospitalBaltimoreUSA

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