[The effects of tamoxifen on human hepatocellular carcinoma cell proliferation and transforming growth factor-beta1 expression].

Jung Woo Shin, Young-Hwa Chung, Moo In Park, Jeong A Kim, Min Hee Choi, Yoon Jung Lee, Soo Hyung Ryu, Neung Hwa Park, Han Chu Lee, Yung Sang Lee, Dong Jin Suh, Eun Sil Yu
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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 (0.1micro 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.

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[他莫昔芬对人肝癌细胞增殖及转化生长因子β 1表达的影响]。
背景/目的:他莫昔芬已在肝细胞癌(HCC)患者中进行了试验,但其抑制机制尚不清楚。在本研究中,我们评估了他莫昔芬对HCC细胞生长和转化生长因子- β 1 (tgf - β 1)表达的影响,tgf - β 1是HCC生长中重要的细胞因子。方法:将Hep 3B细胞培养于无雌激素的培养基中,加入0.1 μ M、0.5 μ M、1 μ M、5 μ M、10 μ M的他莫昔芬,培养6 d。每天计数活细胞,ELISA法测定上清中tgf - β 1浓度。结果:低浓度(0.1 μ M)他莫昔芬治疗后,肝癌细胞存活数较对照组明显增加(2.59 × 10(7)比1.97 × 107;结论:在体外实验中,不同浓度的他莫昔芬对肝癌细胞增殖的影响不同,但可在一定程度上抑制tgf - β 1的表达。他莫昔芬对TGF-beta1表达的影响可能抑制体内过表达TGF-beta1的hcc的生长和进展。
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