Gao Jiankun, Wang Gu, Wu Jingrong, Zuo Yu, Zhang Jing, Jin Xintian
Department of Basic Medical Science, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan 621000, China.
Department of Thoracic Oncosurgery, Jilin Province Cancer Hospital, Changchun, Jilin 130012, China.
Mol Ther Oncolytics. 2019 Feb 5;12:214-223. doi: 10.1016/j.omto.2019.01.006. eCollection 2019 Mar 29.
Arsenic trioxide (ATO) has been found to exert its anti-cancer activity in various human malignancies. In our previous report, we have shown that ATO inhibited cell growth and invasion via downregulation of Skp2 in pancreatic cancer (PC) cells. It has been extensively demonstrated that microRNAs (miRNAs) play a pivotal role in tumorigenesis. ATO might induce PC cell apoptosis and regulate Skp2 downregulation through the regulation of miRNAs. One study has demonstrated that miR-330-5p exerts a tumor-suppressive function in PC cell lines. Here, we investigated the role of miRNA-330-5p in ATO-mediated anti-tumor activity and explored whether ATO could regulate miR-330-5p in PC cells. We found that ATO treatment upregulated the expression of miR-330-5p. Moreover, miR-330-5p inhibitor rescued the ATO-mediated tumor-suppressive function. The combination of miR-330-5p mimic with ATO reduced cell growth, motility, and invasion, and enhanced apoptosis to a greater degree in PC cells. This study suggests that the combination of miR-330-5p mimic with ATO may be a potential therapeutic strategy for the treatment of PC.
三氧化二砷（ATO）已被发现可在多种人类恶性肿瘤中发挥抗癌活性。在我们之前的报告中，我们已经表明ATO通过下调胰腺癌（PC）细胞中的Skp2来抑制细胞生长和侵袭。大量研究表明，微小RNA（miRNA）在肿瘤发生中起关键作用。ATO可能通过调节miRNA诱导PC细胞凋亡并调节Skp2的下调。一项研究表明，miR-330-5p在PC细胞系中发挥肿瘤抑制功能。在此，我们研究了miRNA-330-5p在ATO介导的抗肿瘤活性中的作用，并探讨了ATO是否可以调节PC细胞中的miR-330-5p。我们发现ATO处理上调了miR-330-5p的表达。此外，miR-330-5p抑制剂挽救了ATO介导的肿瘤抑制功能。miR-330-5p模拟物与ATO的组合在PC细胞中降低了细胞生长、运动性和侵袭性，并在更大程度上增强了细胞凋亡。这项研究表明，miR-330-5p模拟物与ATO的组合可能是治疗PC的潜在治疗策略。
