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Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway.
Tumour Biol. 2017 May; 39(5):1010428317697562.TB

Abstract

Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway-related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V-fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V-fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin + BEZ235 group, the cell viability was lower and the apoptosis rate was higher than those of the control and monotherapy groups. Compared with the cisplatin group, the tunicamycin + cisplatin group showed a relatively higher growth inhibition rate; the growth inhibition rate substantially increased in the tunicamycin + cisplatin + BEZ235 group than the tunicamycin + cisplatin group. The apoptosis rate was highest in tunicamycin + cisplatin + BEZ235 group, followed by tunicamycin + cisplatin group and then cisplatin group. Our study provide evidence that endoplasmic reticulum stress activated by tunicamycin could promote breast cancer cell autophagy and apoptosis and enhance chemosensitivity of MCF-7 cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

Authors+Show Affiliations

1 Department of Pathology, Xinxiang Medical University, Xinxiang, P.R. China.2 Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China.1 Department of Pathology, Xinxiang Medical University, Xinxiang, P.R. China.3 School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, P.R. China.4 Department of Immunology, Xinxiang Medical University, Xinxiang, P.R. China.5 Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, P.R. China.5 Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, P.R. China.3 School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28459209

Citation

Zhong, Jia-Teng, et al. "Effects of Endoplasmic Reticulum Stress On the Autophagy, Apoptosis, and Chemotherapy Resistance of Human Breast Cancer Cells By Regulating the PI3K/AKT/mTOR Signaling Pathway." Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine, vol. 39, no. 5, 2017, p. 1010428317697562.
Zhong JT, Yu J, Wang HJ, et al. Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway. Tumour Biol. 2017;39(5):1010428317697562.
Zhong, J. T., Yu, J., Wang, H. J., Shi, Y., Zhao, T. S., He, B. X., Qiao, B., & Feng, Z. W. (2017). Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway. Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine, 39(5), 1010428317697562. https://doi.org/10.1177/1010428317697562
Zhong JT, et al. Effects of Endoplasmic Reticulum Stress On the Autophagy, Apoptosis, and Chemotherapy Resistance of Human Breast Cancer Cells By Regulating the PI3K/AKT/mTOR Signaling Pathway. Tumour Biol. 2017;39(5):1010428317697562. PubMed PMID: 28459209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway. AU - Zhong,Jia-Teng, AU - Yu,Jian, AU - Wang,Hai-Jun, AU - Shi,Yu, AU - Zhao,Tie-Suo, AU - He,Bao-Xia, AU - Qiao,Bin, AU - Feng,Zhi-Wei, PY - 2017/5/2/entrez PY - 2017/5/2/pubmed PY - 2017/6/8/medline KW - Endoplasmic reticulum stress KW - MCF-7 cells KW - PI3K/AKT/mTOR signaling pathway KW - apoptosis KW - autophagy KW - chemotherapy resistance SP - 1010428317697562 EP - 1010428317697562 JF - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JO - Tumour Biol VL - 39 IS - 5 N2 - Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway-related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V-fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V-fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin + BEZ235 group, the cell viability was lower and the apoptosis rate was higher than those of the control and monotherapy groups. Compared with the cisplatin group, the tunicamycin + cisplatin group showed a relatively higher growth inhibition rate; the growth inhibition rate substantially increased in the tunicamycin + cisplatin + BEZ235 group than the tunicamycin + cisplatin group. The apoptosis rate was highest in tunicamycin + cisplatin + BEZ235 group, followed by tunicamycin + cisplatin group and then cisplatin group. Our study provide evidence that endoplasmic reticulum stress activated by tunicamycin could promote breast cancer cell autophagy and apoptosis and enhance chemosensitivity of MCF-7 cells by inhibiting the PI3K/AKT/mTOR signaling pathway. SN - 1423-0380 UR - https://www.unboundmedicine.com/medline/citation/28459209/Effects_of_endoplasmic_reticulum_stress_on_the_autophagy_apoptosis_and_chemotherapy_resistance_of_human_breast_cancer_cells_by_regulating_the_PI3K/AKT/mTOR_signaling_pathway_ L2 - https://journals.sagepub.com/doi/10.1177/1010428317697562?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -