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1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma growth, but not parathyroid hormone
M E Cohen-Solal1, Z Bouizar, M A Denne
1INSERM U349, Centre Viggo Petersen, Hôpital Lariboisière, Paris, France.
Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|September 1, 1995
Summary
Dexamethasone and 1,25 dihydroxyvitamin D (1,25[OH]2D) reduce Walker carcinoma tumor growth in vivo. While both decrease parathyroid hormone related protein (PTHrP) levels, only 1,25[OH]2D significantly lowers PTHrP mRNA expression.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Parathyroid hormone related protein (PTHrP) is implicated in breast cancer development.
- 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) are known to suppress PTHrP mRNA expression in cell lines.
Purpose of the Study:
- To investigate the in vivo effects of 1,25(OH)2D and DEX on PTHrP secretion and Walker carcinoma (WC) tumor development.
- To assess the impact of these steroids on tumor weight, plasma calcium, and PTHrP levels in a rat model.
Main Methods:
- Walker carcinoma cells were xenografted into Fisher rats.
- Rats were treated with vehicle, 1,25(OH)2D, or DEX.
- Tumor weight, plasma calcium, plasma PTHrP, and tumor PTHrP mRNA levels were measured.
Main Results:
- Both 1,25(OH)2D and DEX significantly reduced tumor weight compared to controls.
- Hypercalcemia was observed in vehicle and 1,25(OH)2D treated rats, while DEX treatment decreased plasma calcium.
- Plasma PTHrP levels decreased in treated groups, but tumor PTHrP mRNA was significantly reduced only by 1,25(OH)2D.
Conclusions:
- Dexamethasone and 1,25(OH)2D effectively inhibit Walker carcinoma tumor growth in vivo.
- These steroids reduce PTHrP secretion, but 1,25(OH)2D uniquely decreases steady-state PTHrP mRNA levels in the tumor.