In vivo and in vitro growth stimulation of murine hepatoma cells by glucocorticoid.
An increased level of glucocorticoid receptors has been found in hepatoma. The aim of this study was to determine the in vivo effect of glucocorticoid on the growth of murine hepatoma cells. In vitro cell growth was determined by MTT assay, while cell cycle progression was assayed with flow cytometry. For in vivo experiments, ML-3 and Hepa 1-6 cells were implanted in BALB/c and SCID mice, respectively. Each mouse received 4 subcutaneous injections of hydrocortisone and/or RU486 after tumor implantation. We found that glucocorticoid treatment of ML-3 and Hepa 1-6 cells in vitro resulted in an increase in cell growth which was partially inhibited by RU486, a glucocorticoid antagonist. Glucocorticoid treatment enhanced the cell cycle progression of ML-3 cells. The incidence of ML-3 tumor in the hydrocortisone group was significantly higher than that of the saline, RU486, or hydrocortisone plus RU486 groups. RU486 partially blocked the hydrocortisone-stimulated growth of hepatoma. Further study showed that glucocorticoid treatment of SCID mice also stimulated Hepa 1-6 tumor growth. In conclusion, our results indicated that glucocorticoid directly stimulated hepatoma growth and this stimulation was not the result of immune suppression. Glucocorticoids may play an important role in regulating the growth of hepatoma.
Lui
Wing-Yiu
WY
Department of Surgery, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Chi
Chin-Wen
CW
Chang
Yuh-Fang
YF
Chu
Hoi-Weng
HW
Hsieh
Chih-Chang
CC
Yin
Pen-Hui
PH
Liu
Tsung-Yun
TY
Ou
Ying-Ru
YR
P'eng
Fang-Ku
FK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology
D005938:Glucocorticoids; D006133:Growth Substances; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D006854:Hydrocortisone