Chao Wang, Xuexin Zhang, Jun Su, Ming Chu, Hua Jin, Li Guofu, Tan Chunlei, Xu Wanhai
Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of Neurosurgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Exp Ther Med. 2014 Apr;7(4):923-928. doi: 10.3892/etm.2014.1544. Epub 2014 Feb 13.
Resveratrol (RE), a phytoestrogen, has antiestrogenic properties. Estrogen plays a key role in the development and progression of pituitary prolactinoma. Moreover, RE is a potent cancer chemopreventive agent that inhibits the initiation, promotion and progression of carcinogenesis. The present study investigated the antitumor effects of RE on GH3 pituitary tumor cells. A concentration- and treatment duration-dependent biphasic effect of RE on the proliferation of the GH3 cells was demonstrated. After three days of treatment, RE stimulated proliferation at low concentrations and inhibited proliferation at high concentrations. However, when the treatment duration was reduced to 6 h, RE inhibited proliferation in a concentration-dependent manner. In addition, RE induced apoptosis with the activation of caspase-3 and -8, and decreased the percentage of prolactin (PRL)-immunopositive GH3 cells. Furthermore, RE suppressed expression of the PRL gene and inhibited the cell proliferation and PRL synthesis induced by 17β-estradiol (E2). In GH3 cells, the proliferation response exhibited higher sensitivity to E2 compared with the PRL response; by contrast, the PRL response was more sensitive to RE than the proliferation response was. These results indicate that RE, an antiestrogenic compound, exerts its antitumor effect on GH3 cells through the suppression of GH3 cell growth and through the inhibition of PRL synthesis. The RE-induced cell apoptosis was shown to be caspase-dependent. Therefore, the present study provides support for the use of RE in the chemoprevention and chemotherapy of pituitary prolactinoma.
白藜芦醇（RE）是一种植物雌激素，具有抗雌激素特性。雌激素在垂体催乳素瘤的发生和发展中起关键作用。此外，RE是一种有效的癌症化学预防剂，可抑制致癌作用的起始、促进和进展。本研究调查了RE对GH3垂体肿瘤细胞的抗肿瘤作用。结果显示RE对GH3细胞增殖具有浓度和处理时间依赖性的双相效应。处理三天后，低浓度的RE刺激增殖，高浓度时则抑制增殖。然而，当处理时间缩短至6小时时，RE以浓度依赖性方式抑制增殖。此外，RE通过激活caspase-3和-8诱导细胞凋亡，并降低催乳素（PRL）免疫阳性GH3细胞的百分比。此外，RE抑制PRL基因的表达，并抑制17β-雌二醇（E2）诱导的细胞增殖和PRL合成。在GH3细胞中，与PRL反应相比，增殖反应对E2表现出更高的敏感性；相反，PRL反应对RE比增殖反应更敏感。这些结果表明，作为一种抗雌激素化合物，RE通过抑制GH3细胞生长和抑制PRL合成对GH3细胞发挥抗肿瘤作用。RE诱导的细胞凋亡显示为caspase依赖性。因此，本研究为RE在垂体催乳素瘤的化学预防和化疗中的应用提供了支持。
