Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

Abstract Background Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains u...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xingyun Liu, Jia Yang, Chengwei Yang, Xiang Huang, Mingming Han, Fang Kang, Juan Li
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Morphine Non-small cell lung cancer µ-Opioid receptor Malignant biological behavior Src/mTOR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/f8c14728bcc24cd29c687b464f1b8012
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f8c14728bcc24cd29c687b464f1b8012
record_format	dspace
spelling	oai:doaj.org-article:f8c14728bcc24cd29c687b464f1b80122021-11-28T12:36:46ZMorphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway10.1186/s12935-021-02334-81475-2867https://doaj.org/article/f8c14728bcc24cd29c687b464f1b80122021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02334-8https://doaj.org/toc/1475-2867Abstract Background Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer. Methods Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment. Results Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells. Conclusion Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.Xingyun LiuJia YangChengwei YangXiang HuangMingming HanFang KangJuan LiBMCarticleMorphineNon-small cell lung cancerµ-Opioid receptorMalignant biological behaviorSrc/mTORNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Morphine Non-small cell lung cancer µ-Opioid receptor Malignant biological behavior Src/mTOR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Morphine Non-small cell lung cancer µ-Opioid receptor Malignant biological behavior Src/mTOR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Xingyun Liu Jia Yang Chengwei Yang Xiang Huang Mingming Han Fang Kang Juan Li Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
description	Abstract Background Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer. Methods Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment. Results Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells. Conclusion Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.
format	article
author	Xingyun Liu Jia Yang Chengwei Yang Xiang Huang Mingming Han Fang Kang Juan Li
author_facet	Xingyun Liu Jia Yang Chengwei Yang Xiang Huang Mingming Han Fang Kang Juan Li
author_sort	Xingyun Liu
title	Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
title_short	Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
title_full	Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
title_fullStr	Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
title_full_unstemmed	Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
title_sort	morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the mor/src/mtor pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f8c14728bcc24cd29c687b464f1b8012
work_keys_str_mv	AT xingyunliu morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway AT jiayang morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway AT chengweiyang morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway AT xianghuang morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway AT mingminghan morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway AT fangkang morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway AT juanli morphinepromotesthemalignantbiologicalbehaviorofnonsmallcelllungcancercellsthroughthemorsrcmtorpathway
_version_	1718407930330480640

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

Ejemplares similares