PDF(Pubmed)
Abstract：
Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and β-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.
摘要：
舌鳞状细胞癌（TSCC）在口腔鳞状细胞癌中占有很高的比例。TSCC的特点是淋巴结转移率高，化疗耐药，预后差。因此,需要有效的治疗策略来改善患者的预后.褪黑素（MT）是一种天然吲哚化合物，在多种癌症中具有抗肿瘤作用。本研究主要探讨MT在TSCC细胞中的作用及机制。研究结果表明，MT可以抑制CRL-1623细胞的细胞增殖。Westernblot分析表明MT下调细胞周期蛋白B1和上调P21蛋白。MT还显示下调Zeb1，Wnt5A/B的表达，和β-catenin蛋白和上调E-cadherin抑制CRL-1623细胞的迁移。MT还促进了ATF4、ATF6、Bip、CRL-1623细胞中的BAP31和CHOP导致内质网应激，诱导CRL-1623细胞自噬和凋亡。Western印迹显示MT可以促进Bax的表达,LC3和Beclin1蛋白并抑制p62的表达。我们在MT处理的细胞中筛选了差异表达的长链非编码RNA（lncRNA），发现MALAT1和H19的表达降低。此外，MT在接种CRL-1623细胞的裸鼠中抑制肿瘤生长。这些结果表明，MT可以诱导自噬，促进细胞凋亡，并为TSCC的治疗提供潜在的天然化合物。
