Research Papers:

This article has been retracted. Retraction in: Oncotarget. 2019; 10:4252-4252.

Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway

Xin-Shuang Yu, Juan Du, Yu-Jun Fan, Feng-Jun Liu, Li-Li Cao, Ning Liang, De-Guo Xu and Jian-Dong Zhang _

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Oncotarget. 2016; 7:76827-76839. https://doi.org/10.18632/oncotarget.12718

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Xin-Shuang Yu1, Juan Du1,2, Yu-Jun Fan3, Feng-Jun Liu1, Li-Li Cao2, Ning Liang1, De-Guo Xu1, Jian-Dong Zhang1

1Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, P.R. China

2Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, P.R. China

3Medical Management Service Center of Shandong Provincial Health and Family Planning Commission, Jinan 250014, P.R. China

Correspondence to:

Jian-Dong Zhang, email: [email protected]

Juan Du, email: [email protected]

Keywords: endoplasmic reticulum stress, PI3K/AKT/mTOR signaling pathway, small cell lung cancer, autophagy, apoptosis

Received: June 21, 2016     Accepted: September 28, 2016     Published: October 18, 2016


Objective: This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway.

Results: The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h. Compared with the blank group, the tunicamycin, BEZ235 and tunicamycin + BEZ235 groups exhibited decreased expressions of p-PI3K, p-AKT and p-mTOR, and increased expressions of autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis proteins (Bax and procaspase-3), and the most obvious changes were observed in the tunicamycin + BEZ235 group.

Materials and Methods: CCK-8 assay was applied to select the best cell line from five SCLC cell lines (NCI-H446, H69, H526, H146 and H209). Finally, NCI-H446 and H69 cells were selected for further experiments. NCI-H446/CDDP and H69/CDDP were selected and divided into the blank group, tunicamycin (an ESR inducer) group, BEZ235 (inhibitors of PI3K/AKT/mTOR pathway) group and tunicamycin + BEZ235 group. Cell apoptosis was detected by flow cytometry. Autophagy was observed by fluorescence microscopy and flow cytometry. Western blotting was used to detect the expressions of ERS-related proteins, autophagy-related proteins, apoptosis-related proteins and PI3K/AKT/mTOR pathway-related proteins.

Conclusions: Our findings provide evidence that the activation of ERS could promote autophagy and apoptosis and reverse chemoresistance of human SCLC cells by inhibiting the PI3K/AKT/mTOR pathway.

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