Low-dose DNA-demethylating agent enhances the chemosensitivity of cancer cells by targeting cancer stem cells via the upregulation of microRNA-497
Low-dose DNA-demethylating agent enhances the chemosensitivity of cancer cells by targeting cancer stem cells via the upregulation of microRNA-497
复制标题
低剂量 DNA 去甲基化剂通过上调 microRNA-497 靶向癌症干细胞，从而增强癌细胞的化疗敏感性
DOI：
10.1007/s00432-016-2157-9
复制
发表时间：
2016-07-01
影响因子：
3.6
通讯作者：
Han, Weidong
中科院分区：
文献类型：
--
作者：
Liu, Lin;Chen, Lin;Han, Weidong
DNA去甲基化剂地西他滨（decitabine）已在恶性血液病和实体瘤的治疗中显示出良好的临床疗效，但其抗肿瘤作用的机制尚不完全清楚。采用肿瘤球体形成试验评价低剂量地西他滨对肿瘤起始干细胞的影响，我们观察到无毒的低剂量地西他滨治疗后，各种癌细胞的化疗敏感性增强。此外，低剂量地西他滨治疗抑制了癌症起始细胞的自我更新，并抑制了多能性标志物的表达。值得注意的是，低剂量的地西他滨能够增加癌症干细胞的化疗敏感性，可能是通过上调miRNA-497，据报道，miRNA-497在多种癌症中被下调并促进细胞凋亡。这些结果表明，DNA去甲基化剂可以靶向癌症干细胞，并通过调节microRNA的内源性表达来逆转其化疗耐药性。
The DNA-demethylating agent decitabine has shown clinical response for the treatment of hematological malignancies and solid tumors, while the mechanisms underlying its antitumor capacity are not fully understood.The sensitivities of cancer cells to different chemotherapeutic drugs, such as cisplatin, paclitaxel, and 5-FU, were detected. The tumor sphere formation assay was used to evaluate the effects of low-dose decitabine on cancer-initiating stem cells.We observed that the chemotherapy sensitivity of various cancer cells was enhanced following non-toxic low-dose decitabine treatment. Moreover, low-dose decitabine treatment suppressed the self-renewal of cancer-initiating cells and inhibited the expression of pluripotency markers. Strikingly, low-dose decitabine was able to augment chemosensitivity in cancer stem cells, likely by the upregulation of miRNA-497, which was reported to be downregulated and to have promoted cell apoptosis in multiple cancers.These results indicated that the DNA-demethylating agent could target cancer stem cells and reverse their chemotherapeutic resistance by regulating the endogenous expression of microRNAs.