[The effects of tamoxifen on human hepatocellular carcinoma cell proliferation and transforming growth factor-beta1 expression].
OBJECTIVE
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 (0.1micro M) compared with that of the control (2.59x10(7) vs. 1.97x107; 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 (10micro 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.
Shin
Jung Woo
JW
Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Chung
Young-Hwa
YH
Park
Moo In
MI
Kim
Jeong A
JA
Choi
Min Hee
MH
Lee
Yoon Jung
YJ
Ryu
Soo Hyung
SH
Park
Neung Hwa
NH
Lee
Han Chu
HC
Lee
Yung Sang
YS
Suh
Dong Jin
DJ
Yu
Eun Sil
ES
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
D018931:Antineoplastic Agents, Hormonal; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013629:Tamoxifen