Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells.
Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells.
复制标题
DOI：
10.1016/j.canlet.2015.04.028
复制
发表时间：
2015-08-01
期刊：
影响因子：
9.7
通讯作者：
Sun, Shi-Yong
中科院分区：
文献类型：
--
作者：
Yao, Weilong;Yue, Ping;Zhang, Guojing;Owonikoko, Taofeek K.;Khuri, Fadlo R.;Sun, Shi-Yong
Human non-small cell lung cancer (NSCLC) displays activated MEK/ERK signaling due to a high frequency of K-Ras mutation and is thus a potential candidate for MEK-targeted therapy. The current study focuses on demonstrating the activity of MEK162, a MEK inhibitor under clinical testing, against NSCLC and exploring possible mechanism-driven strategies to enhance its therapeutic efficacy. MEK162 inhibits the growth of human NSCLC cell lines with varied potencies through induction of G1 cell cycle arrest and apoptosis. Moreover, it induces autophagy and accordingly the combination of MEK162 with the autophagy inhibitor, chloroquine, synergistically inhibits the growth of NSCLC cells and enhances apoptosis. MEK162 activates Akt signaling while effectively inhibiting MEK/ERK signaling. Accordingly, the combination of MEK162 and BKM120, a pan PI3K inhibitor, abrogates induced Akt activation and significantly augments therapeutic efficacy against the growth of NSCLC cells both in vitro and in vivo. Hence our findings warrant further evaluation of these rational combinations in the clinic.
登录
查看更多内容
影响因子：
3.7
作者：
Hofmann I;Weiss A;Elain G;Schwaederle M;Sterker D;Romanet V;Schmelzle T;Lai A;Brachmann SM;Bentires-Alj M;Roberts TM;Sellers WR;Hofmann F;Maira SM
通讯作者：
Maira SM
影响因子：
11.2
作者：
Gopal YN;Deng W;Woodman SE;Komurov K;Ram P;Smith PD;Davies MA
通讯作者：
Davies MA
影响因子：
3.6
作者：
Sun, SY;Zhou, ZM;Khuri, FR
通讯作者：
Khuri, FR
影响因子：
8
作者：
Sun, SY;Yue, P;Lotan, R
通讯作者：
Lotan, R
影响因子：
8
作者：
Chen X;Wu Q;Tan L;Porter D;Jager MJ;Emery C;Bastian BC
通讯作者：
Bastian BC