|Table of Contents|

Small molecule inhibitor Torin-2 induces growth inhibition and apoptosis of small cell lung cancer NCI-H446 cell lines

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2020 02
Page:
185-189
Research Field:
Publishing date:

Info

Title:
Small molecule inhibitor Torin-2 induces growth inhibition and apoptosis of small cell lung cancer NCI-H446 cell lines
Author(s):
Mou Han; Zhao Xiangxuan; Ke Weiwei; Wang Hongbo; Lu Zaiming
Department of Radiology，Shengjing Hospital of China Medical University，Liaoning Shenyang 110004,China.
Keywords:
mTOR; Torin-2; chemotherapy; small cell lung cancer; anti-cancer
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2020.02.002
Abstract:
Objective:To investigate the effects of small molecule inhibitor Torin-2 on the growth and apoptosis of human small cell lung carcinoma NCI-H446 cells and explore the underlying mechanism.Methods:NCI-H446 cells in logarithmic growth phase were treated with different concentrations of Torin-2 or 1 μmol/L for 0,12,24,36 and 48 h in vitro.The cell morphology was observed under the microscope to assess apoptosis reflecting by detached floating cells.Cell growth inhibition was evaluated by cloning formation assays.MTS assay was used to test cell proliferation inhibition or cell viability decrease.Cell cycle blockage was measured by flow cytometry (FCM).Primary antibodies including mTOR,p-mTOR(Ser2448),p-Akt(Ser473),Cyclin-B1,Cyclin-D1,Cyclin-E1,and Cleaved Caspase-3 were used to detect protein levels through Western blot.Results:Compared to the control group,Torin-2 inhibited the growth and proliferation of NCI-H446 cells in a concentration- or time-dependent manner.We found that Torin-2 incubation triggered apoptosis and growth inhibition by blocking cell cycle in the G0/G1 phase and the G2/M phase (P＜0.05).Moreover，mechanism analysis revealed that Torin-2 not only reduced phosphorylation activation of mTOR and Akt,but decreased Cyclin-D1,Cyclin-E1,whereas there was no effects on Cyclin-B1.Cleaved Caspase-3 activation further showed that Torin-2 was able to induce apoptosis in lung cancer cells.Conclusion:Torin-2 single treatment can potentially exert anti-cancer effects by triggering growth and proliferation inhibition and apoptosis in human small lung cancer cells.

References:

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Memo

Memo:
National Natural Science Foundation of China（No.81771947，31371425，31240025）;国家自然科学基金(编号:81771947，31371425，31240025);辽宁省自然科学基金(编号:20180551061)
Last Update: 2019-11-29