Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo

B. M. Evers, E. B. Thompson, Courtney Townsend, J. L. Lawrence, B. Johnson, G. Srinivasan, J. C. Thompson

Research output: Contribution to journalArticle

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Abstract

Glucocorticoids are effective in the treatment of certain leukemias and lymphomas, but their effects on the growth of several solid tumors have not been determined. We report here that cortivazol (CVZ), a potent synthetic glucocorticoid, inhibits the growth of a hamster pancreatic adenocarcinoma, H2T, in vivo. CVZ regulation of glucocorticoid receptor (GR) expression was followed as a specific molecular correlate. H2T cells were injected into check pouches of male Syrian golden hamsters, where they formed readily measurable tumors. Two studies were performed. In the first, hamsters were randomized to three groups immediately after injection of tumor cells: control, CVZ (0.1 μg/g body wt), or CVZ (0.3 μg/g body wt). Injections of either CVZ or its vehicle were administered on a 14-day cycle of 5 treatment days, followed by 9 days off treatment. Tumors were measured and areas calculated weekly. On day 48, the hamsters were killed and the tumors excised, weighed, and analyzed for DNA, RNA, and protein content. In the second study, randomization and treatment schedule were as before, except that on day 33 the hamsters were killed, tumors were excised and weighed, and total RNA from the tumors was isolated. GR mRNA content was determined by filter hybridization with a 32P-labeled GR cDNA probe, and the signal normalized by reprobing for α-tubulin as an invariant, independent signal. At either dose, CVZ significantly inhibited H2T tumor area and weight and DNA, RNA, and protein content. Body weights of animals treated with CVZ were not significantly decreased as compared with controls. In addition, GR mRNA in H2T cells was increased approximately twofold by CVZ. These results suggest that the positive induction of GRs in H2T may correlate with the inhibition of tumor growth. CVZ deserves further examination as a useful adjuvant treatment for certain pancreatic cancers.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalPancreas
Volume8
Issue number1
StatePublished - 1993

Fingerprint

Glucocorticoid Receptors
Pancreatic Neoplasms
Cricetinae
Growth
Neoplasms
RNA
Glucocorticoids
Therapeutics
cortivazol
Messenger RNA
Injections
DNA
Mesocricetus
Tubulin
Random Allocation
Tumor Burden
Lymphoma
Appointments and Schedules
Leukemia
Proteins

Keywords

  • Cortivazol
  • Glucocorticoid receptor
  • Pancreatic cancer

ASJC Scopus subject areas

  • Endocrinology
  • Gastroenterology

Cite this

Evers, B. M., Thompson, E. B., Townsend, C., Lawrence, J. L., Johnson, B., Srinivasan, G., & Thompson, J. C. (1993). Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo. Pancreas, 8(1), 7-14.

Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo. / Evers, B. M.; Thompson, E. B.; Townsend, Courtney; Lawrence, J. L.; Johnson, B.; Srinivasan, G.; Thompson, J. C.

In: Pancreas, Vol. 8, No. 1, 1993, p. 7-14.

Research output: Contribution to journalArticle

Evers, BM, Thompson, EB, Townsend, C, Lawrence, JL, Johnson, B, Srinivasan, G & Thompson, JC 1993, 'Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo', Pancreas, vol. 8, no. 1, pp. 7-14.
Evers, B. M. ; Thompson, E. B. ; Townsend, Courtney ; Lawrence, J. L. ; Johnson, B. ; Srinivasan, G. ; Thompson, J. C. / Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo. In: Pancreas. 1993 ; Vol. 8, No. 1. pp. 7-14.
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abstract = "Glucocorticoids are effective in the treatment of certain leukemias and lymphomas, but their effects on the growth of several solid tumors have not been determined. We report here that cortivazol (CVZ), a potent synthetic glucocorticoid, inhibits the growth of a hamster pancreatic adenocarcinoma, H2T, in vivo. CVZ regulation of glucocorticoid receptor (GR) expression was followed as a specific molecular correlate. H2T cells were injected into check pouches of male Syrian golden hamsters, where they formed readily measurable tumors. Two studies were performed. In the first, hamsters were randomized to three groups immediately after injection of tumor cells: control, CVZ (0.1 μg/g body wt), or CVZ (0.3 μg/g body wt). Injections of either CVZ or its vehicle were administered on a 14-day cycle of 5 treatment days, followed by 9 days off treatment. Tumors were measured and areas calculated weekly. On day 48, the hamsters were killed and the tumors excised, weighed, and analyzed for DNA, RNA, and protein content. In the second study, randomization and treatment schedule were as before, except that on day 33 the hamsters were killed, tumors were excised and weighed, and total RNA from the tumors was isolated. GR mRNA content was determined by filter hybridization with a 32P-labeled GR cDNA probe, and the signal normalized by reprobing for α-tubulin as an invariant, independent signal. At either dose, CVZ significantly inhibited H2T tumor area and weight and DNA, RNA, and protein content. Body weights of animals treated with CVZ were not significantly decreased as compared with controls. In addition, GR mRNA in H2T cells was increased approximately twofold by CVZ. These results suggest that the positive induction of GRs in H2T may correlate with the inhibition of tumor growth. CVZ deserves further examination as a useful adjuvant treatment for certain pancreatic cancers.",
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