Abstract:
AIM:Previous study has shown that endometrial cancers with LKB1 inactivation are highly responsive to mTOR inhibitors. In this study we examined the effect of LKB1 gene status on mTOR inhibitor responses in non-small cell lung cancer (NSCLC) cells. METHODS:Lung cancer cell lines Calu-1, H460, H1299, H1792, and A549 were treated with the mTOR inhibitors rapamycin or everolimus (RAD001). The mTOR activity was evaluated by measuring the phosphorylation of 4EBP1 and S6K, the two primary mTOR substrates. Cells proliferation was measured by MTS or sulforhodamine B assays. RESULTS:The basal level of mTOR activity in LKB1 mutant A549 and H460 cells was significantly higher than that in LKB1 wild-type Calu-1 and H1792 cells. However, the LKB1 mutant A549 and H460 cells were not more sensitive to the mTOR inhibitors than the LKB1 wild-type Calu-1 and H1792 cells. Moreover, knockdown of LKB1 gene in H1299 cells did not increase the sensitivity to the mTOR inhibitors. Treatment with rapamycin or RAD001 significantly increased the phosphorylation of AKT in both LKB1 wild-type and LKB1 mutant NSCLC cells, which was attenuated by the PI3K inhibitor LY294002. Furthermore, RAD001 combined with LY294002 markedly enhanced the growth inhibition on LKB1 wild-type H1792 cells and LKB1 mutant A549 cells. CONCLUSION:LKB1 gene inactivation in NSCLC cells does not increase the sensitivity to the mTOR inhibitors. The negative feedback activation of AKT by mTOR inhibition may contribute to the resistance of NSCLC cells to mTOR inhibitors.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Xiao P,Sun LL,Wang J,Han RL,Ma Q,Zhong DSdoi
10.1038/aps.2015.19subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1107-12issue
9eissn
1671-4083issn
1745-7254pii
aps201519journal_volume
36pub_type
杂志文章abstract::Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
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journal_title:Acta pharmacologica Sinica
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
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abstract:AIM:To investigate the effect of cholecystokinin octapeptide (CCK-8) on the diacylglycerol-protein kinase C (DAG-PKC) signaling pathway in rat pulmonary interstitial macrophages (PIM) stimulated by lipopolysaccaride (LPS). METHODS:The PIM from rat lung tissues were isolated using the collagenase digestion method combi...
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doi:10.1111/j.1745-7254.2005.00217.x
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abstract:AIM:To develop a robust, cell-based, high-content screening (HCS) assay based on receptor internalization for the identification of novel modulators of the epidermal growth factor receptor (EGFR). METHODS:Agonist-induced receptor internalization is part of the signaling cascade of EGFR. Fluorescent-tagged epidermal gr...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00640.x
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2007-10-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
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pub_type: 杂志文章,评审
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更新日期:2003-05-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00474.x
更新日期:2007-02-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00581.x
更新日期:2007-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00526.x
更新日期:2005-02-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00331.x
更新日期:2006-08-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2008.18
更新日期:2009-02-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00581-5
更新日期:2021-01-25 00:00:00
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pub_type: 杂志文章,评审
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