1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma growth, but not parathyroid hormone related protein secretion.
Parathyroid hormone related protein (PTHrP) is produced by several breast cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been shown to decrease PTHrP mRNA expression in several cell lines. We therefore tested the in vivo effect of both steroids on PTHrP secretion and tumor development of the Walker carcinoma (WC). WC cells were injected subcutaneously in Fisher rats which were simultaneously treated with either vehicle, or 1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight was significantly decreased in the 2 treated-groups as compared to the control group. Vehicle treated-rats developed hypercalcemia, which was also observed in rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly decreased in the DEX-treated group compared to vehicle-treated rats. In a dose-effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats not implanted with WC, but was required to decrease the tumor weight in implanted rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were significantly decreased, but there was a similar correlation between PTHrP plasma level and tumor weight in the three groups. Indeed, the cytosolic PTHrP content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D decrease WC tumor development in vivo, but do not change the PTHrP secretion by the remaining tumor although steady state PTHrP mRNA content level is decreased by 1,25(OH)2D.
Cohen-Solal
M E
ME
INSERM U349, Centre Viggo Petersen, Hôpital Lariboisière, Paris, France.
Bouizar
Z
Z
Denne
M A
MA
Graulet
A M
AM
Gueris
J
J
Bracq
S
S
Jullienne
A
A
de Vernejoul
M C
MC
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002279:Carcinoma 256, Walker / Q000378:metabolism* / Q000473:pathology*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D044162:Parathyroid Hormone-Related Protein; D003907:Dexamethasone; D002117:Calcitriol; D002118:Calcium