Meng Qing-Wei, Zhao Chang-Hong, Xi Yu-Hui, Cai Li, Sun Li-Chun, Sui Guang-Jie
Fourth Department of Medical Oncology, Affiliated Tumor Hospital, Harbin Medical University, Harbin 150040, China.
Zhonghua Zhong Liu Za Zhi. 2006 Jul;28(7):503-6.
To investigate the anti-tumor effect and the mechanism of down-regulation of HER - 2 by cabamazepine in SKBR - 3 cells , a breast cancer cell line with HER - 2 over - expression.
Western blotting was performed to evaluate the Her-2 expression level. The mRNA level of HER-2 was detected by RT-PCR. Immunoprecipitation was applied to detect the chaperon function and acetylation level of HSP90. The viability of cells was tested by MTT assay.
Cabamazepine treatment down-regulated HER-2 expression. Only HER-2 protein level decrease was observed with 10 micromol/L cabamazepine treatment, but both protein and mRNA expressions were inhibited by 100 micromol/L cabamazepine. Cabamazepine treatment could induce a higher acetylation level of HSP90 and destroy its chaperon function. Cabamazepine exerted synergism with Herceptin in promoting HER-2 protein degradation and synergism or potentiation with Herceptin or 17-AAG in inhibition of proliferation.
Cabamazepine can reduce the expression of HER-2 and show a synergistic effect with Herceptin or 17-AAG. There may be potential benefits of carbamazepine for cancer therapy in future. HER-2;
研究卡马西平对HER-2过表达的乳腺癌细胞系SKBR-3细胞的抗肿瘤作用及其下调HER-2的机制。
采用蛋白质免疫印迹法评估Her-2表达水平。通过逆转录聚合酶链反应检测HER-2的mRNA水平。应用免疫沉淀法检测热休克蛋白90（HSP90）的伴侣功能和乙酰化水平。采用MTT法检测细胞活力。
卡马西平处理可下调HER-2表达。10 μmol/L卡马西平处理仅观察到HER-2蛋白水平降低，但100 μmol/L卡马西平可抑制蛋白和mRNA表达。卡马西平处理可诱导HSP90更高的乙酰化水平并破坏其伴侣功能。卡马西平与赫赛汀在促进HER-2蛋白降解方面发挥协同作用，并与赫赛汀或17-烯丙基氨基-17-去甲氧基格尔德霉素在抑制增殖方面发挥协同或增强作用。
卡马西平可降低HER-2表达，并与赫赛汀或17-烯丙基氨基-17-去甲氧基格尔德霉素显示协同效应。未来卡马西平在癌症治疗中可能具有潜在益处。HER-2；
