Morphine promotes migration and lung metastasis of mouse melanoma cells
Morfina promove migração e metástase pulmonar de células de melanoma de camundongo
Golnaz Vaseghi, Nasim Dana, Ahmad Ghasemi, Reza Abediny, Ismail Laher, Shaghayegh Haghjooy Javanmard
Abstract
Background
Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation.
Methods
Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules.
Results
Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05).
Conclusion
Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.
Keywords
Resumo
Introdução
A morfina é um agente analgésico usado para o tratamento da dor oncológica. Tem havido preocupações recentes de que as propriedades imunossupressoras da morfina também possam promover a metástase do câncer. A morfina é um agonista do receptor tipo toll-4 (TLR4) que tem um papel duplo no desenvolvimento do câncer. O papel promotor ou inibidor da morfina na progressão do câncer permanece controverso. Nós investigamos os efeitos da morfina na migração e metástase de células de melanoma através da ativação de TLR4.
Métodos
Células de melanoma de camundongo (B16F10) foram tratadas apenas com morfina (0, 0,1, 1 e 10 μM) ou em combinação com um inibidor de TLR4 (morfina 10 μM +CLI-095 1 μM) por 12 ou 24 horas. A migração de células foi analisada por ensaios de migração transwell. Vinte camundongos machos C57BL/6 foram inoculados com células B16F10 através do ventrículo esquerdo do coração e então divididos aleatoriamente em dois grupos (n = 10 cada) que receberam morfina (10 mg.kg−1, sub-q) ou injeção de PBS por 21 dias (grupo controle). Os animais foram sacrificados e seus pulmões removidos para avaliação de nódulos metastáticos.
Resultados
A morfina (0,1, 1 e 10 μM) aumentou a migração celular após 12 horas (p < 0,001) e após 24 horas de tratamento com morfina (10 μM) (p < 0,001). O tratamento com CLI-095 suprimiu a migração em comparação com células tratadas apenas com morfina (p < 0,001). Nódulos metastáticos no grupo tratado com morfina (64 nódulos) foram significativamente maiores do que no grupo controle (40 nódulos) (p < 0,05).
Conclusão
A morfina aumenta a migração e metástase de células de melanoma de camundongo ativando TLR4.
Palavras-chave
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