title: Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer.
abstract: Morphine is an opioid analgesic drug commonly used for pain relief in cancer patients. Here, we report that morphine enhances the mammosphere forming capacity and increases the expression of stemness-related transcription factors Oct4, Sox2 and Nanog. Treatment with morphine leads to enrichment of a side population fraction in MCF-7 cells and the CD44+/CD24(-/low) population in BT549 cells. Consistently, morphine activates Wnt/β-catenin signaling to induce epithelial to mesenchymal transition and promotes metastasis. Moreover, morphine decreases the sensitivity of traditional anti-cancer drugs in breast cancer cells. Nalmefene, an antagonist of morphine, reverses morphine-induced cancer stem cell properties and chemoresistance in breast cancer. In addition, nalmefene abolishes morphine enhancing tumorigenesis in a NOD/SCID mouse model. In conclusion, our findings demonstrate that morphine contributes to chemoresistance via expanding the population of cancer stem cells and promotes tumor growth, thereby revealing a novel role of morphine and providing some new guides in clinical use of morphine.
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.|Department of Anesthesia, The First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
authors: Dong-Ge
authors: DG
authors: Niu
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors: Fei
authors: F
authors: Peng
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors: Zhong
authors: Z
authors: Guan
authors: Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors: Hai-Dong
authors: HD
authors: Zhao
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.|Department of Anesthesia, The First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
authors: Jing-Lin
authors: JL
authors: Li
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.|Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors: Kai-Li
authors: KL
authors: Wang
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors: Ting-Ting
authors: TT
authors: Li
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors: Yan
authors: Y
authors: Zhang
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors: Fei-Meng
authors: FM
authors: Zheng
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.|Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors: Fan
authors: F
authors: Xu
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.|Department of Anesthesia, The First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
authors: Qian-Ni
authors: QN
authors: Han
authors: Department of Anesthesia, The First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
authors: Peng
authors: P
authors: Gao
authors: Department of Anesthesia, The First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
authors: Qing-Ping
authors: QP
authors: Wen
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors: Quentin
authors: Q
authors: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009020:Morphine / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*
chemical_list: D009020:Morphine