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Pharmaceutical biology

Triptolide modulates the sensitivity of K562/A02 cells to adriamycin by regulating miR-21 expression.


PMID 22957792

Abstract

Multidrug-resistance is a serious obstacle encountered in leukemia treatment. Recent studies have shown microRNA-21 (miR-21) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. In our previous studies, we found triptolide (TPL) could enhance adriamycin-induced cytotoxicity and apoptosis in K562/A02 cells. In the present study, we investigated the mechanism of TPL on the sensitivity of K562/A02 cells to adriamycin. Cell viability was assessed by methyl thiazolyl tetrazolium (MTT) assay. Expression of mature miR-21 was determined by SYBER green PCR. The miR-21 mimics and inhibitors were chemically synthesized and transfected into K562 cells or K562/A02 cells. PTEN protein levels was determined by western blots. PTEN promoter activity was measured by luciferase assays. TPL (5 nmol/L) increased the sensitivity of K562/A02 to adriamycin. When adriamycin was combined with 5 nmol/L TPL, the mean apoptotic population of K562/A02 cells was increased from 4.3 to 18.5%, respectively. K562/A02 cells showed a significant reduction in miR-21 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) expressions after TPL treatment. K562/A02 cells that were transfected with the miR-21 inhibitor had a significantly higher PTEN protein level than the control. K562 cells that were pre-treated with PTEN siRNA had increased survival rate compared to the control group. Our findings indicated that triptolide modulates the sensitivity of K562/A02 cells to adriamycin by regulating miR-21 expression. Triptolide inhibited miR-21 expression and enhanced PTEN levels in K562/A02 cells.