Melatonin induces cell apoptosis in Mia PaCa-2 cells via the suppression of nuclear factor-κB and activation of ERK and JNK: A novel therapeutic implication for pancreatic cancer
Melatonin induces cell apoptosis in Mia PaCa-2 cells via the suppression of nuclear factor-κB and activation of ERK and JNK: A novel therapeutic implication for pancreatic cancer
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DOI：
10.3892/or.2016.5100
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发表时间：
2016-11-01
期刊：
影响因子：
4.2
通讯作者：
Fan, Mengdi
中科院分区：
文献类型：
--
作者：
Li, Weimin;Wu, Jiansheng;Fan, Mengdi
褪黑素由松果体合成并释放到血液中。在过去的几年里，一些研究表明褪黑素具有抗癌特性；然而，抗肿瘤特性背后的机制尚不清楚，特别是在胰腺癌中。因此，在本研究中，我们研究了褪黑素对人胰腺癌细胞系MIA PaCa-2的抗肿瘤作用，并探讨其生物学机制。褪黑素处理MIA PaCa-2细胞，我们使用CCK-8测定法评估细胞活力。流式细胞术观察细胞凋亡情况，western blot检测蛋白表达。我们的研究发现，褪黑激素抑制MIA PaCa-2细胞活力，抑制集落形成，减少细胞迁移和侵袭，诱导细胞凋亡。我们的研究结果表明，褪黑素治疗抑制NF-kappa bp65的激活。此外，褪黑激素激活了丝裂原激活的蛋白激酶途径（c-jun n-末端激酶和细胞外调节激酶1/2），增加了Bax蛋白表达和caspase-3切割，降低了Bcl-2蛋白表达。这些新进展表明，褪黑素在抗癌治疗中发挥着潜在的作用，并可能在未来作为一种有效的治疗药物。
Melatonin is synthesized by the pineal gland and is released into the blood. In the last several years, some studies have shown that melatonin has anticancer properties; however, the mechanisms behind the antitumour traits are unclear, especially in pancreatic cancer. Therefore, in the present study, we investigated the antitumour effects of melatonin on the human pancreatic carcinoma cell line MIA PaCa-2 and explored its biological mechanisms. MIA PaCa-2 cells were treated with melatonin, and we used a CCK-8 assay to evaluate the cell viability. We also used flow cytometry to observe cell apoptosis and western blot analysis to assess the protein expression. Our study found that melatonin inhibited cell viability, suppressed colony formation and reduced cell migration and invasion and induced cell apoptosis in MIA PaCa-2 cells. Our results showed that melatonin treatment inhibited NF-kappa B p65 activation. Moreover, melatonin treatment activated the mitogen-activated protein kinase pathways (c-jun N-terminal kinase and extracellular-regulated kinase 1/2), which increased Bax protein expression and caspase-3 cleavage and decreased Bcl-2 protein expression. These new developments demonstrate that melatonin plays a potential role in anticancer treatment and may act as an effective therapeutic agent in the future.