Li Jiasu, Gao Hongmei, Meng Lingxu, Yin Lin
Department of Stomatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Tumour Biol. 2017 Jun;39(6):1010428317708697. doi: 10.1177/1010428317708697.
Mithramycin exhibits certain anticancer effects in glioma, metastatic cerebral carcinoma, malignant lymphoma, chorionic carcinoma and breast cancer. However, its effects on salivary adenoid cystic carcinoma remain unclear. Here, we report that mithramycin significantly inhibited epithelial-to-mesenchymal transition and invasion in human salivary adenoid cystic carcinoma cell lines. The underlying mechanism for this activity was further demonstrated to involve decreasing the expression of the transcription factors specificity protein 1 and SNAI1. Specificity protein 1 is a pro-tumourigenic transcription factor that is overexpressed in SACC-LM and SACC-83 cells, and its expression is inhibited by mithramycin. Moreover, chromatin immunoprecipitation assays showed that specificity protein 1 induced SNAI1 transcription through direct binding to the SNAI1 promoter. In summary, this study uncovered the mechanism through which mithramycin inhibits epithelial-to-mesenchymal transition and invasion in salivary adenoid cystic carcinoma cell lines, namely, via downregulating specificity protein 1 and SNAI1 expression, which suggests mithramycin may be a promising therapeutic option for salivary adenoid cystic carcinoma.
光辉霉素在胶质瘤、转移性脑癌、恶性淋巴瘤、绒毛膜癌和乳腺癌中表现出一定的抗癌作用。然而，其对涎腺腺样囊性癌的作用尚不清楚。在此，我们报告光辉霉素显著抑制人涎腺腺样囊性癌细胞系中的上皮-间质转化和侵袭。该活性的潜在机制进一步证明涉及降低转录因子特异性蛋白1（SP1）和SNAI1的表达。SP1是一种促肿瘤发生的转录因子，在SACC-LM和SACC-83细胞中过表达，其表达受到光辉霉素的抑制。此外，染色质免疫沉淀试验表明，SP1通过直接结合SNAI1启动子诱导SNAI1转录。总之，本研究揭示了光辉霉素抑制涎腺腺样囊性癌细胞系上皮-间质转化和侵袭的机制，即通过下调SP1和SNAI1表达，这表明光辉霉素可能是涎腺腺样囊性癌一种有前景的治疗选择。
