Baicalein Inhibites Multiple Myeloma Cells Proliferation and Migration by Interfering Wnt Signaling Pathway

Abstract 5019 Background: The Wnt/β-catenin signaling pathway has been implicated in a variety of tumor cell survival and proliferation, including myeloma cells. It can facilitate myeloma cell proliferation by upregulating the expression of many related genes, such as c-myc, cyclin D1, MMP and so on. We have previously demonstrated that Baicalein, a important component of Scutellaria radix from Huang-Lian-Jie-Du-Tang(HLJDT), can inhibit cell proliferation and induce cell death in myeloma cell through suppressing NF-κB activation (Ma Z, et al., Blood, 2005, 105(8): 3312–3318). In clinic, we found that HLJDT had a very good effective in multiple myeloma(MM) patients treatment (data not show). But, the precise molecular mechanism of HLJDT exerts its anti-tumor effects remains poorly understood. Here we further evaluated alternative mechanisms which is responsible for inhibition myeloma cell proliferation and migration by baicalein. Methods: Myeloma cell lines, RPMI8226 and U266 cells, were used for the analysis. MTT assay was used to assess cell viability in RPMI8226 and U266 cells which were exposed to baicalein with different concentrations and time period. Immunofluorescence assay and western blot analysis were used to assess β-catenin protein expression in MM cell lines. Transwell chamber migration assay was used to assess migration ability of myeloma cells treated with different concentrations of baicalein. RT-PCR analysis was used to assess β-catenin, c-myc, cyclin D1 and integrin β7 mRNA expression. Results: Baicalein can inhibit the MM cell lines proliferation in a dose- and time-dependent manner as measured by MTT assay. Immunofluorescence images and western bloting revealed that treatment of baicalein decreased the β-catenin protein expression level in myeloma cells. The mRNA expression level of β-catenin, c-myc and cyclin D1 was also decreased by baicalein treatment. In addition, we found that baicalein has an ability to inhibit the migration of MM cell llines, RPMI8226 and U266 cell, by decreasing the integrin β7 mRNA expression in a dose-dependent manner. Conclusion: Baicalein can inhibit myeloma cell proliferation is related to downregulation of β-catenin, c-myc and cyclin D1 genes expression, and the inhibition of myeloma ia associated with suppression of integrin β7 gene expression. Thus, HLJDT may have a potential of clinical applications in MM patient treatment. Disclosures: No relevant conflicts of interest to declare.