Kafami Marzieh, Vaseghi Golnaz, Haghjooy Javanmard Shaghayegh, Mahdavi Manijeh, Dana Nasim, Esmalian-Afyouni Nazgol, Gohari Ali
Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Adv Biomed Res. 2023 Jun 28;12:149. doi: 10.4103/abr.abr_107_22. eCollection 2023.
The Toll-like receptor 4 (TLR4) gene promotes migration in adenocarcinoma cells. Morphine is an agonist for TLR4 that has a dual role in cancer development. The promoter or inhibitor role of morphine in cancer progression remains controversial. This study aims to evaluate the effects of morphine on the TLR4, myeloid differentiation primary response protein 88-dependent (MyD88), and nuclear factor-kappa B (NF-κB) expressions in the human MDA-MB-231 breast cancer cell line.
The cells were examined after 24 hours of incubation with morphine using the Boyden chamber system. TLR4, MyD88, and NF-κB mRNA expressions were assessed using quantitative real-time polymerase chain reaction (RT-PCR). The concentration of interleukin-2 beta was also measured using the ELISA assay.
According to the findings, three doses of morphine (0.25, 1.25, and 0.025 μM) increased the expression of the TLR4 and NF-κB genes, whereas no significant change was observed in the mRNA expression of MyD88. Furthermore, treatment with morphine and lipopolysaccharide (LPS) significantly decreased the expression of TLR4, MyD88, and NF-κB. However, no significant change was observed in interleukin 2 beta concentration.
These findings confirmed the excitatory effects of morphine on TRL4 expression and the MYD88 signaling pathway .
Toll样受体4（TLR4）基因促进腺癌细胞迁移。吗啡是TLR4的激动剂，在癌症发展中具有双重作用。吗啡在癌症进展中的促进或抑制作用仍存在争议。本研究旨在评估吗啡对人MDA-MB-231乳腺癌细胞系中TLR4、髓样分化初级反应蛋白88依赖性（MyD88）和核因子-κB（NF-κB）表达的影响。
使用博伊登室系统，将细胞与吗啡孵育24小时后进行检测。采用定量实时聚合酶链反应（RT-PCR）评估TLR4、MyD88和NF-κB mRNA表达。还使用酶联免疫吸附测定（ELISA）法测量白细胞介素-2β的浓度。
根据研究结果，三剂量的吗啡（0.25、1.25和0.025μM）增加了TLR4和NF-κB基因的表达，而MyD88的mRNA表达未观察到显著变化。此外，吗啡和脂多糖（LPS）处理显著降低了TLR4、MyD88和NF-κB的表达。然而，白细胞介素2β浓度未观察到显著变化。
这些发现证实了吗啡对TRL4表达和MYD88信号通路的兴奋作用。
