内质网应激在褪黑素诱导的肾上腺皮质癌细胞凋亡和抑制侵袭迁移中的作用。
Role of Endoplasmic Reticulum Stress in Melatonin-induced Apoptosis and Inhibition of Invasion and Migration in Adrenocortical Carcinoma Cells.
机构信息
Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, Guangxi, China.
Department of General Practice, Liuzhou Workers' Hospital, 545007 Liuzhou, Guangxi, China.
出版信息
Discov Med. 2024 Nov;36(190):2214-2223. doi: 10.24976/Discov.Med.202436190.203.
BACKGROUND
Melatonin, a hormone synthesized by the pineal gland and released into the blood, seems to have anti-tumor properties. However, the mechanisms of the anti-cancer effect of melatonin are largely unknown. This study investigated the anti-tumor activity of melatonin in adrenocortical carcinoma (ACC) and analyzed its molecular mechanisms.
METHODS
Different concentrations of melatonin were added to ACC cells and . Cell viability was appraised via Cell Counting Kit-8 (CCK-8) assay, cell migration and invasion were appraised via wound healing assay and transwell assay, and cell apoptosis was appraised via flow cytometry. The levels of nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) pathway proteins (c-Jun N-terminal kinase (JNK) and p38) and endoplasmic reticulum stress-related proteins (C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78)) were appraised via western blot.
RESULTS
Melatonin reduced the proliferation rate, migration rate, and invasion rate of ACC cells, and significantly increased apoptosis of ACC cells in contrast with the Control Check (CK) group. Moreover, melatonin intervention reduced NF-κB/MAPK signal routing (JNK and p38) and endoplasmic reticulum stress (CHOP and GRP78). Treatment with the NF-κB/MAPK pathway inhibitor NF-κB/MAPK-IN-1 (3.48 μM) enhanced the inhibitory effects of melatonin on the activity of ACC cells and increased apoptosis. The subcutaneous tumor model (SW-13) in nude mice further confirmed that melatonin induced apoptosis of ACC cells by reducing endoplasmic reticulum stress, and NF-κB/MAPK signal routing was involved in this effect.
CONCLUSION
Melatonin induces apoptosis of ACC cells by reducing endoplasmic reticulum stress, and this effects was may be related to the NF-κB/MAPK signal routing. Melatonin may be an effective anti-tumor agent and have great potential as an adjuvant therapy in the future.
背景
褪黑素是由松果体合成并释放入血的激素，似乎具有抗肿瘤特性。然而，褪黑素的抗癌作用机制在很大程度上尚不清楚。本研究探讨了褪黑素在肾上腺皮质癌（ACC）中的抗肿瘤活性，并分析了其分子机制。
方法
将不同浓度的褪黑素添加到 ACC 细胞中。通过细胞计数试剂盒-8（CCK-8）测定评估细胞活力，通过划痕愈合试验和 Transwell 试验评估细胞迁移和侵袭，通过流式细胞术评估细胞凋亡。通过 Western blot 评估核因子 kappa B（NF-κB）/丝裂原活化蛋白激酶（MAPK）通路蛋白（c-Jun N-末端激酶（JNK）和 p38）和内质网应激相关蛋白（C/EBP 同源蛋白（CHOP）和葡萄糖调节蛋白 78（GRP78））的水平。
结果
褪黑素降低了 ACC 细胞的增殖率、迁移率和侵袭率，并与对照检查（CK）组相比，显著增加了 ACC 细胞的凋亡。此外，褪黑素干预降低了 NF-κB/MAPK 信号转导（JNK 和 p38）和内质网应激（CHOP 和 GRP78）。用 NF-κB/MAPK 通路抑制剂 NF-κB/MAPK-IN-1（3.48 μM）处理增强了褪黑素对 ACC 细胞活性的抑制作用，并增加了凋亡。裸鼠皮下肿瘤模型（SW-13）进一步证实，褪黑素通过减少内质网应激诱导 ACC 细胞凋亡，NF-κB/MAPK 信号转导参与了这一作用。
结论
褪黑素通过减少内质网应激诱导 ACC 细胞凋亡，这种作用可能与 NF-κB/MAPK 信号转导有关。褪黑素可能是一种有效的抗肿瘤药物，具有作为未来辅助治疗的巨大潜力。
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