In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC

• 作 者: Xu-Dong Xiang Jing Yu Gao-Feng Li Lin Xie Heng Li
• 机 构: Department of Thoracic Surgery,Third Affiliated Hospital of Kunming Medical University,Department of
• 出 处: Asian Pacific Journal of Tropical Medicine
• 发表日期: 2014年05期
• 关键词: mTOR cytometry signaling cycle purchased arrest polyclonal inhibit blocking tetr

Objective:To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.Methods:MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549.Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h.RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.Results:MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells.Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phase cell cycle arrest,which was time-dependent(P<0.05).RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.Conclusions:mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC,which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549.The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.

Objective: To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC. Methods: MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549. Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h. RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy. Results: MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells. Flow cytometry showed when everolimus could induce apoptosis and induce G0 / G1 phase cell cycle arrest, which was time-dependent (P <0.05) .RT-PCR showed everolimus could increase PTEN and 4EBP1 expression. Conclusions: mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC, which can not reverse the resistance effect of EGFR-TKI resistant cell line A549. The relationship between EGFR / AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.