Gambogenic Acid Exerts Antitumor Activity By Mir-21 Regulation in Hypoxic Multiple Myeloma Cells

Multiple myeloma (MM) remains one of the incurable diseases despite novel therapies; microRNA-21 (miR-21) is one of the key oncomirs overexpressed in MM and plays a key role in multiple malignancy-related processes. It has been shown that miR-21 expression is not only closely related to the development of tumor, but also to the hypoxic environment. Gambogenic acid (GNA) is the major active ingredient of gamboge, which has been shown to possess antitumor effect both in vitro and in vivo study. In this study, we investigated the effects of GNA on human MM U266 cells. It has been found that GNA-induced apoptosis is correlated with miR-21/PTEN pathway. When MM cells were subjected to hypoxia, the level of miR-21 increased and GNA treatment constrained this upregulation by reducing HIF-1α accumulation and STAT3 phosphorylation. Moreover, the in vivo study revealed that intravenous injection of GNA once every other day for 2 weeks could suppress tumor volumes by inhibiting the miR-21/PTEN pathway. Therefore, GNA could be a new and potent therapeutic agent against human MM.