Low-dose DNA-demethylating agent enhances the chemosensitivity of cancer cells by targeting cancer stem cells via the upregulation of microRNA-497

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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