Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China.
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
Int J Mol Sci. 2021 May 9;22(9):5022. doi: 10.3390/ijms22095022.
Ovarian cancer is a fatal gynecological cancer because of a lack of early diagnosis, which often relapses as chemoresistant. Trichodermin, a trichothecene first isolated from , is an inhibitor of eukaryotic protein synthesis. However, whether trichodermin is able to suppress ovarian cancer or not was unclear. In this study, trichodermin (0.5 µM or greater) significantly decreased the proliferation of two ovarian cancer cell lines A2780/CP70 and OVCAR-3. Normal ovarian IOSE 346 cells were much less susceptible to trichodermin than the cancer cell lines. Trichodermin predominantly inhibited ovarian cancer cells by inducing G0/G1 cell cycle arrest rather than apoptosis. Trichodermin decreased the expression of cyclin D1, CDK4, CDK2, retinoblastoma protein, Cdc25A, and c-Myc but showed little effect on the expression of p21, p27, or p16. c-Myc was a key target of trichodermin. Trichodermin regulated the expression of Cdc25A and its downstream proteins via c-Myc. Overexpression of c-Myc attenuated trichodermin's anti-ovarian cancer activity. In addition, trichodermin decelerated tumor growth in BALB/c nude mice, proving its effectiveness in vivo. These findings suggested that trichodermin has the potential to contribute to the treatment of ovarian cancer.
卵巢癌是一种致命的妇科癌症，因为缺乏早期诊断，往往会产生耐药性而复发。木霉素是一种从 中首次分离出来的三萜烯，是真核生物蛋白质合成的抑制剂。然而，木霉素是否能够抑制卵巢癌尚不清楚。在这项研究中，木霉素（0.5µM 或更高）显著降低了两种卵巢癌细胞系 A2780/CP70 和 OVCAR-3 的增殖。正常卵巢 IOSE 346 细胞对木霉素的敏感性明显低于癌细胞系。木霉素主要通过诱导 G0/G1 细胞周期停滞而不是凋亡来抑制卵巢癌细胞。木霉素降低了细胞周期蛋白 D1、CDK4、CDK2、视网膜母细胞瘤蛋白、Cdc25A 和 c-Myc 的表达，但对 p21、p27 或 p16 的表达影响不大。c-Myc 是木霉素的关键靶标。木霉素通过 c-Myc 调节 Cdc25A 及其下游蛋白的表达。c-Myc 的过表达减弱了木霉素的抗卵巢癌活性。此外，木霉素在 BALB/c 裸鼠中减缓了肿瘤生长，证明了其在体内的有效性。这些发现表明木霉素有可能有助于治疗卵巢癌。
