Glucocorticoids promote the development of azoxymethane and dextran sulfate sodium-induced colorectal carcinoma in mice.

Abstract

BACKGROUND:

Stress has been suggested as a promoter of tumor growth and development. Glucocorticoids (GCs) are the main stress hormones and widely prescribed as drugs. However, the effect of GCs on the development and progression of colorectal carcinoma (CRC) is unclear.

METHODS:

We evaluated the effect of corticosterone (CORT) on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in the colorectum of C57BL/6 strain mice. Plasma level of CORT was detected by radioimmunoassay. The expression of proliferation markers (Ki-67 and PCNA), nuclear factor (NF)-κB p65 and phosphoto-p65 (P-p65), as well as cyclooxygenase (COX)-2 were determined by immunohistochemistry. Inflammation in colorectum was evaluated by histopathology.

RESULTS:

CORT feeding in drinking water of mice not only significantly elevated plasma CORT concentration, but also significantly increased the incidence and neoplasms burden (number and size of neoplasms) in colorectum. CORT also significant enhanced the expression of cell proliferation marker (Ki-67 and PCNA), NF-κB p65 and P-p65 as well as COX-2 in colorectal neoplasm of AOM/DSS-treated mice.

CONCLUSION:

In this study, we have found for the first time that CORT at stress level potentially promotes the growth and development of AOM/DSS-induced colorectal adenoma and carcinoma in mice. Up-regulation of NF-κB and COX-2 may be involved in the promoting effect of CORT.

• Authors: Bo Li, Yan Wang, Lijuan Yin, Gaoxiang Huang, Yi Xu, Jie Su, Liye Ma, Jian Lu
• Journal: BMC cancer (BMC Cancer) Vol. 19 Issue 1 Pg. 94 (Jan 21 2019) ISSN: 1471-2407 [Electronic] England
• PMID: 30665389 (Publication Type: Journal Article)

Chemical References

• Glucocorticoids
• Ki-67 Antigen
• Proliferating Cell Nuclear Antigen
• Transcription Factor RelA
• Dextran Sulfate
• Cyclooxygenase 2
• Azoxymethane

Topics

• Animals
• Azoxymethane (toxicity)
• Carcinogenesis (drug effects, metabolism)
• Colorectal Neoplasms (blood, chemically induced, metabolism)
• Cyclooxygenase 2 (biosynthesis)
• Dextran Sulfate (toxicity)
• Drug Synergism
• Glucocorticoids (toxicity)
• Humans
• Immunohistochemistry
• Ki-67 Antigen (biosynthesis)
• Male
• Mice, Inbred C57BL
• Proliferating Cell Nuclear Antigen (biosynthesis)
• Transcription Factor RelA (biosynthesis)