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05 May 2018 : Laboratory Research

Baicalein Inhibits Proliferation of Myeloma U266 Cells by Downregulating IKZF1 and IKZF3

Xiao-Ping Liu1ABC*, Li He2CD, Qiu-Ping Zhang3CDE, Xian-Tao Zeng1EF, Shang-Qin Liu4DEG

DOI: 10.12659/MSM.907058

Med Sci Monit 2018; 24: LBR2809-2817

Abstract

BACKGROUND: Baicalein can suppress the growth of multiple tumors, including multiple myeloma (MM), but the exact mechanisms remains elusive. Here, we investigated the exact mechanisms of the anti-myeloma activity of baicalein.

MATERIAL AND METHODS: Proliferation and rates of apoptosis of myeloma U266 cells exposed to baicalein were detected. Microarray, polymerase chain reaction (PCR) assay, and Western blot analysis were applied to evaluate the mRNA and protein levels of associated molecules. Survival analysis of IKZF1 and IKZF3 was conducted as well.

RESULTS: Baicalein suppressed the growth and stimulated apoptosis of myeloma U266 cells in a dose- and time-dependent way. Baicalein increased mRNA level of CRBN, and further studies suggested that baicalein downregulated IKZF1 and IKZF3 on a post-transcriptional level. Although the differences did not reach statistical significance, IKZF1 and IKZF3 were associated with poor overall survival.

CONCLUSIONS: Our results suggest that baicalein suppresses the growth and promotes apoptosis of myeloma U266 cells through downregulating IKZF1 and IKZF3. Baicalein increased the expression of CRBN, which might exert a reversion effect on resistance of IMiDs. MM patients in IKZF1 and IKZF3 low-expression groups had better overall survival than those in IKZF1 and IKZF3 high-expression groups. Thus, the present results indicate that baicalein might be a therapeutic choice for targeting IKZF1 and IKZF3.

Keywords: Multiple Myeloma, Scutellaria baicalensis

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750