西妥昔单抗
细胞凋亡
癌症研究
化学
未折叠蛋白反应
PI3K/AKT/mTOR通路
蛋白激酶B
生物
医学
癌症
内科学
生物化学
结直肠癌
作者
Ning Kang,Shijie Cao,Benke Jiang,Qiang Zhang,Paul Owusu Donkor,Yan Zhu,Feng Qiu,Xiumei Gao
标识
DOI:10.1016/j.tiv.2020.104885
摘要
Cetuximab plus oridonin showed a synergistic way to kill laryngeal squamous cell carcinoma (LSCC), as been reported previously. The present work further mechanistically extended action of the synergistic effects of combination treatment. Firstly, two LSCC cells displayed higher sensitivity to oridonin, whereas both low EGFR expression tumor cells and EGFR knockdown LSCC cells were less sensitive to oridonin. Next, cetuximab/oridonin significantly enhanced the mitochondrial apoptosis through NF-κB. Meanwhile, PI3K/Akt and JAK2/STAT3 pathways are associated with the nucleus translocation of NF-κB by combination treatment. Additionally, cetuximab enhanced oridonin-promoted ER stress-related apoptosis. Interestingly, both ER stress and mitochondrial apoptosis by combination treatment are abrogated by ROS scavenger. Furthermore, oridonin/cetuximab induced ROS production after 1.5 h, followed by G2/M arrest and apoptosis, indicating that ROS generation might be an early and key event. Taken together, cetuximab enhances oridonin-induced ER stress and mitochondrial apoptotic pathway, which contributes to the synergistic antitumor effects of cetuximab/oridonin.
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