Glaucocalyxin B Attenuates Ovarian Cancer Cell Growth and Cisplatin Resistance In Vitro via Activating Oxidative Stress

青萼素 B 通过激活氧化应激减弱卵巢癌细胞生长和顺铂耐药性

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作者:Tingting Zhang, Chenxin Xu, Peisen Zheng, Xiaoxian Zhang, Chenyu Qiu, Fengjiao Wu, Jundixia Chen, Zhongxiang Xiao, Jiandong Zhu, Jingjing Zhang, Peng Zou, Daoyong Ni

Abstract

Ovarian cancer is one of the fatal gynecological cancers around the world. Cisplatin is the first-line chemotherapy drug for the clinical treatment of ovarian cancer. However, many patients with ovarian cancer are still suffering from resistance to cisplatin. Therefore, the new drug combinations or treatment strategies for ovarian cancer are urgently needed. Glaucocalyxin B (GLB), a diterpenoid isolated from the aerial parts of Rabdosia japonica, has shown antitumor activity in some tumors. However, the mechanisms by which GLB inhibits ovarian cancer remain unclear. In the present study, we showed that GLB potently inhibits ovarian cancer cell growth in a dose-dependent manner. Furthermore, we found that GLB has a notably synergistic antitumor effect with cisplatin. Mechanistically, we found that GLB enhances the sensitivity of ovarian cancer cells to cisplatin via increasing reactive oxygen species (ROS) levels, the phosphorylation of c-Jun N-terminal kinase (JNK), and DNA damage. Interestingly, a synergistic inhibitory effect of GLB with cisplatin was also observed in the cells which were resistance to cisplatin. Together, these data suggest that GLB can sensitize ovarian cancer cells to cisplatin by increasing ROS levels.

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