Korean J Hepatol.  2003 Mar;9(1):10-16.

The Effects of Tamoxifen on Human Hepatocelluar Carcinoma Cell Proliferation and Transforming Growth Factor-beta1 Expression

• Shin JW
• Chung YH
• Park MI
• Kim JA
• Choi MH
• Lee YJ
• Ryu SH
• Park NH
• Lee HC
• Lee YS
• Suh DJ
• Yu ES

Abstract

BACKGROUND/AIMS: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-beta1 (TGF-beta1) which had been known as an important cytokine in growth of HCC. METHODS: Hep 3B cells were cultivated in estrogen free media with 0.1 micro M, 0.5 micro M, 1 micro M, 5 micro M, and 10 micro M of tamoxifen for 6 days. Viable cells were counted daily and the TGF-beta1 concentrations in supernatant were measured by ELISA method. RESULTS: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1 micro M) compared with that of the control (2.59x10(7) vs. 1.97x10(7); p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10 micro M) compared with that of the control (1.40x10(7) vs. 1.97x10(7); p<0.05). TGF-beta1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. CONCLUSIONS: These results suggest that tamoxifen may suppress TGF-beta1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-beta1 expression may inhibit the growth and progression of HCCs over-expressing TGF-beta1 in vivo.

Keyword

Neoplasm/Liver/Hepatocellular carcinoma; Tamoxifen; Transforming Growth Factor-beta1

MeSH Terms

Antineoplastic Agents, Hormonal/*pharmacology
Carcinoma, Hepatocellular/*metabolism/pathology
Cell Division/drug effects
Cell Line, Tumor/metabolism
Humans
Liver Neoplasms/*metabolism/pathology
Tamoxifen/*pharmacology
Transforming Growth Factor beta/*biosynthesis
Transforming Growth Factor beta1