Scutellarin induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT Signaling Pathways in vitro and in vivo.
Scutellarin induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT Signaling Pathways in vitro and in vivo.
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DOI：
10.7150/jca.25921
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发表时间：
2018
影响因子：
3.9
通讯作者：
Feng B
中科院分区：
文献类型：
--
作者：
Sun C;Li C;Li X;Zhu Y;Su Z;Wang X;He Q;Zheng G;Feng B
非小细胞肺癌（NSCLC）的治愈性分子疗法仍然缺乏。灯盏乙素是从灯盏细辛中提取的活性黄酮，在多种癌症类型中显示出抗肿瘤特性，但其对 NSCLC 的肿瘤抑制作用尚未见报道。在这项研究中，我们发现灯盏花乙素显着抑制NSCLC细胞的增殖，诱导细胞凋亡，并引发自噬。值得注意的是，用抑制剂 HCQ 抑制自噬会减弱灯盏花乙素的抗增殖活性，表明灯盏花乙素诱导的自噬具有抗肿瘤作用。此外，HCQ 治疗可减少灯盏花乙素诱导的细胞凋亡。进一步的研究表明，灯盏花乙素刺激 ERK1/2 的磷酸化，并且用抑制剂 U0126 抑制 ERK1/2 显着减弱灯盏花乙素诱导的自噬。同样，灯盏乙素下调 p-AKT 的表达，而 AKT 抑制剂 MK-2206 诱导自噬。此外，ERK和AKT通路之间还存在串扰。最后，体内异种移植裸鼠实验证明，灯盏花乙素治疗可显着减少小鼠肿瘤中的肿瘤生长，并增加LC3-II和p-ERK1/2的水平，抑制p-AKT。因此，我们的研究首次揭示了灯盏花乙素对NSCLC细胞的抗癌作用，可能为NSCLC患者的治疗提供潜在的新疗法。
Curative molecular therapy for non-small cell lung cancer (NSCLC) is still lacking. Scutellarin, an active flavone extracted from Erigeron breviscapus Hand-Mazz, displays anti-tumor property in diverse cancer types, yet its tumor-suppressive effect on NSCLC is not reported. In this study, we found that scutellarin significantly inhibited the proliferation of NSCLC cells, induced cell apoptosis, and triggered autophagy. Notably, inhibition of autophagy with inhibitor HCQ attenuated the anti-proliferative activity of scutellarin, indicating that scutellarin-induced autophagy is antineoplastic. In addition, HCQ treatment reduced scutellarin-induced apoptosis. Further study demonstrated that scutellarin stimulated phosphorylation of ERK1/2, and inhibition of ERK1/2 with inhibitor U0126 markedly attenuated scutellarin-induced autophagy. Similarly, scutellarin downregulated the expression of p-AKT, and AKT inhibitor MK-2206 induced autophagy. Moreover, there also existed crosstalk between ERK and AKT pathways. Finally, in vivo xenograft nude mice experiment proved that scutellarin treatment significantly reduced tumor growth and increased the levels of LC3-II and p-ERK1/2, suppressed p-AKT in mice tumors. Thus, our study for the first time uncovered the anti-cancer function of scutellarin on NSCLC cells, and might provide a potential novel therapy for treatment of patients with NSCLC.
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影响因子：
11.2
作者：
Bartholomeusz C;Rosen D;Wei C;Kazansky A;Yamasaki F;Takahashi T;Itamochi H;Kondo S;Liu J;Ueno NT
通讯作者：
Ueno NT
SKF-96365 通过抑制钙/CaMKII gamma/AKT 介导的途径激活细胞保护性自噬以延迟结直肠癌细胞的凋亡
影响因子：
9.7
作者：
Jing Z;Sui X;Yao J;Xie J;Jiang L;Zhou Y;Pan H;Han W
通讯作者：
Han W
DOI：
10.1016/j.bbrc.2018.01.052
发表时间：
2018-02-05
影响因子：
3.1
作者：
Li, Xugui;Lu, Qilin;Wang, Guanqing
通讯作者：
Wang, Guanqing
影响因子：
5.6
作者：
Liu G;Pei F;Yang F;Li L;Amin AD;Liu S;Buchan JR;Cho WC
通讯作者：
Cho WC
影响因子：
4.8
作者：
Chen, Chi-Wei;Wu, Ming-Hsi;Lee, Te-Chang
通讯作者：
Lee, Te-Chang