Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway

• Published in: Scientific reports 2024-09, Vol.14 (1), p.21130-9, Article 21130
• Main Authors: Gu, Fulei, Zhou, Yuxuan, Tian, Lili, Chen, Jinyan, Zhang, Can, Huang, Zhangxiang, Yu, Weifeng, Xie, Kangjie
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/67/1612; 692/308; A549 Cells; AKT protein; Animals; Cadherins - metabolism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Disease Progression; Down-Regulation - drug effects; E-cadherin; Gene Expression Regulation, Neoplastic - drug effects; Humanities and Social Sciences; Humans; Immunofluorescence; Immunohistochemistry; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Malignant biological behaviour; Mice; Mice, Nude; Molecular modelling; Morphine; Morphine - pharmacology; multidisciplinary; Naloxone; Naloxone - pharmacology; Non-small cell lung cancer; Non-small cell lung carcinoma; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - drug effects; Small cell lung carcinoma; Survival; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumor cell lines; Tumors; Wound healing; Xenograft Model Antitumor Assays; Xenografts; µ-Opioid receptor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-72198-1

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro ( p