Effects of Luteolin on Biological Behaviors of Colorectal Cancer Stem Cell-like Cells and Related Pathway

OBJECTIVE: To evaluate the effects of luteolin on the growth and metastatic abilities of colorectal cancer stem cell-like cells (CSCLCs). STUDY DESIGN: LoVo cells were cultured in serum-free DMEM/F12 containing cytokines to obtain tumor cell microspheres. The expression rates of markers CD44(+) and CD133(+) on the surfaces of LoVo cells and derived CSCLCs were detected by flow cytometry. CCK-8 and Transwell assays were conducted to detect the proliferative and invasive abilities of CSCLCs. The protein expressions of E-cadherin, Twist, transcription factor 4 (TCF-4), beta-catenin, and matrix metalloproteinase-2 (MMP-2) were detected by Western blotting. The tumor-bearing mouse model was established. Tumor cell microspheres were cultured by LoVo cells in stem cell culture environment, and new microspheres formed after continuous passage. RESULTS: The expression rates of CD44(+) and CD133(+) on CSCLCs were significantly higher than those of LoVo cells. Luteolin effectively inhibited the proliferation and invasion of CSCLCs dose-dependently. It up-regulated the expression of E-cadherin, while it down-regulated those of Twist, beta-catenin, TCF-4, and MMP-2. CONCLUSION: Luteolin had inhibitory effects on the growth and metastasis of colon cancer cells in mice. Luteolin significantly suppresses the invasive and metastatic abilities of CSCLCs derived from colorectal cancer LoVo cells, probably by inhibiting the Wnt/beta-catenin/TCF-4 signaling pathway.