A novel chemotherapeutic arene ruthenium(II) drug Rawq01 altered the effect of microRNA-21 on PTEN/AKT signaling pathway in esophageal cancer cells.

AIM: Organometallic arene Ru(II) complexes have long been considered as most promising substitutes for cisplatinum as an anti-tumor drug, with low toxicity towards human normal cells and high selectivity to tumor cells. In this study, we synthesized a novel arene Ru(II) drug named Rawq01. We evaluated its activity in an in vitro model of esophageal cancer (ESCC) and further explored the cellular signaling pathways altered by Rawq01.

MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphe nyltetrazolium bromide (MTT) assay, colony forming assay and apoptosis assays were used to evaluate the antitumor activity of Rawq01. We treated ESCC cells with Rawq01 alone or combined with microRNA-21(miR-21) and LY294002 to explore whether Rawq01 altered the effect of miR-21 on PTEN/AKT signaling pathway in ESCC cell.

RESULTS: ESCC cells were sensitive to RAWQ01. We also found that Rawq01 up-regulated the expression of PTEN through mir-21 inhibition and therefore inhibited the PI3K-AKT pathway. Furthermore, when we combined Rawq01 treatment with miR-21 inhibitor or LY294002, the inhibitory effect of Rawq01 was significantly enhanced.

CONCLUSION: The effect of miR-21 on PTEN/AKT signaling pathway is abrogated by the novel arene Ru(II) drug Rawq01. Our data may be useful for the future development of a chemosensitizing strategies through manipulating microRNA expression for tumor treatment.