他莫昔芬通过蛋白激酶C拮抗雌激素受体阴性转移性滤泡性甲状腺癌细胞的增殖和侵袭。

Tamoxifen antagonizes proliferation and invasion of estrogen receptor-negative metastatic follicular thyroid cancer cells via protein kinase C.

作者信息

Hoelting T, Duh Q Y, Clark O H, Herfarth C

机构信息

Department of Surgery, University of Heidelberg, Germany.

出版信息

Cancer Lett. 1996 Feb 27;100(1-2):89-93. doi: 10.1016/0304-3835(95)04074-9.

DOI:10.1016/0304-3835(95)04074-9

PMID:8620458

Abstract

Tamoxifen inhibits invasion and growth of estrogen-receptor negative follicular thyroid cancer (FTC) cells in vitro and in vivo. To study the mechanisms involved, we documented the effects of tamoxifen and staurosporine on three metastatic FTC-cell lines. TPA (10 ng/ml) enhanced invasion and growth of FTC by 15% (P < 0.02). Tamoxifen (1.5 micromol/l) inhibited invasion of FTC133 by 36% (FTC236 30%; FTC238 32%; P < 0.01). TPA reversed the tamoxifen-mediated inhibition of invasion by 35% in FTC133 and 30% in FTC238 (P < 0.02). Staurosporine (10 ng/ml) inhibited invasion and growth of all FTC. At 0.1-1 ng/ml it enhanced the inhibitory effects of tamoxifen, but did not further inhibit invasion or growth at higher concentrations. We conclude that the antiproliferative and antiinvasive effects of tamoxifen on follicular thyroid cancer cells are at least partly mediated by an inhibition of protein kinase C.

摘要

他莫昔芬在体外和体内均能抑制雌激素受体阴性的滤泡状甲状腺癌（FTC）细胞的侵袭和生长。为研究其中涉及的机制，我们记录了他莫昔芬和星形孢菌素对三种转移性FTC细胞系的影响。佛波酯（TPA，10 ng/ml）使FTC的侵袭和生长增强了15%（P < 0.02）。他莫昔芬（1.5 μmol/l）使FTC133的侵袭受到36%的抑制（FTC236为30%；FTC238为32%；P < 0.01）。TPA使他莫昔芬介导的FTC133侵袭抑制作用逆转了35%，FTC238中逆转了30%（P < 0.02）。星形孢菌素（10 ng/ml）抑制所有FTC的侵袭和生长。在0.1 - 1 ng/ml时，它增强了他莫昔芬的抑制作用，但在更高浓度时并未进一步抑制侵袭或生长。我们得出结论，他莫昔芬对滤泡状甲状腺癌细胞的抗增殖和抗侵袭作用至少部分是由对蛋白激酶C的抑制介导的。