beta-catenin small interfering RNA successfully suppressed progression of multiple myeloma in a mouse model.

Abstract

beta-catenin is the downstream effector of the Wnt signaling pathway, and it regulates cell proliferation. beta-catenin overexpression correlates positively with prognosis in several types of malignancies. We herein assessed its effects on growth of multiple myeloma cells using a xenograft model. We first investigated the expression of beta-catenin in multiple myeloma cell lines and multiple myeloma cells obtained from patients. Next, we investigated the growth inhibitory effects of beta-catenin small interfering RNA on the growth of multiple myeloma cells in vivo. Six-week-old male BALB/c nu/nu mice were inoculated s.c. in the right flank with 5 x 10(6) RPMI8226 cells, followed by s.c. injections of beta-catenin small interfering RNA, scramble small interfering RNA, or PBS/atelocollagen complex twice a week for a total of eight injections. Significantly higher levels of beta-catenin expression were observed in multiple myeloma cell lines and in samples from patients with multiple myeloma than those found in mononuclear cells obtained from healthy volunteers. In in vivo experiments, no inhibitory effects were observed following treatment with scramble small interfering RNA or PBS/atelocollagen complexes, whereas treatment with beta-catenin small interfering RNA/atelocollagen complex significantly inhibited growth of multiple myeloma tumors (P < 0.05). beta-catenin small interfering RNA treatment inhibited the growth of multiple myeloma tumors in a xenograft model. To our knowledge, this is the first report showing that the treatment with beta-catenin small interfering RNA produces an inhibitory effects on growth of hematologic malignancies in vivo. Because treatment with beta-catenin small interfering RNA inhibited growth of multiple myeloma cells, beta-catenin is the attractive novel target for treating multiple myeloma.