首页|Suppression of AOM/DSS-induced colorectal cancer by scutellarin through downregulation of Wnt signaling pathway activity
Suppression of AOM/DSS-induced colorectal cancer by scutellarin through downregulation of Wnt signaling pathway activity
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
国家科技期刊平台
NETL
NSTL
万方数据
维普
OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer (CAC) and its underlying mechanism based on Wnt/β-catenin signaling pathway. METHODS The mouse model of CAC was estab⁃lished by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by scutellarin treatment, with recording the body weight, diarrhea and hematochezia. After sacrificing the mice, the colorectal length and colorectal tumor were assessed. The levels of pro-inflammatory factors TNF-α and IL-6 in mice's sera were measured by the enzyme-linked immunosorbent assay (ELISA). The colorectal lesions were appraised by hematoxylin and eosin (H&E) staining. Theβ-catenin level in CAC tissues was probed by immunofluorescent analysis. The apoptosis-related genes Bax and Bcl-2, and Wnt signaling pathway-related genes β-catenin, GSK-3β, TCF4, c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR (RT-qPCR). Finally, Western blotting analysis (WB) was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related proteins. RESULTS Scutellarin significantly improved AOM/DSS-caused weight loss, colorectal length shortening, and tumor growth in mice (P<0.01). Meanwhile, colorectal lesions could be substantially alleviated by scutellarin. ELISA results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened (P<0.01). Scutellarin also sharply inhibited the nuclear translocation of β-catenin, as evidenced by the reduction in the nuclear level ofβ-catenin protein. In addition, scutellarin attenuated the mRNA expres⁃sion of Wnt signaling pathway-relatedβ-catenin, TCF4, c-Myc and cyclin D1, whereas it heightened GSK-3βmRNA level. These results were consolidated by WB analysis, which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin, TCF4, c-Myc and cyclin D1, with the increase in GSK-3β protein in CAC tissue. Moreover, scutellarin could induce the apoptosis of CAC, demonstrated by enhanced expression of Bax and diminished expression of Bcl-2 in both mRNA and protein levels. CONCLUSION Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.
State Key Laboratory of Southwestern Chinese Medicine Resources,Department of Pharmacology,ChengduUniversity of Traditional Chinese Medicine,Chengdu 611137,China
Institute of Chinese Medical Sciences,University of Macau,Macao,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaSichuan Provincial Admin?istration of Traditional Chinese Medicine of ChinaExcellent Talent Program of Chengdu University of Traditional Chinese Medicine of ChinaExcellent Talent Program of Chengdu University of Traditional Chinese Medicine of ChinaOpen Research Fund of the State Key Labora?tory of Southwestern Chinese Medicine Resources of China
国家科技期刊平台
NSTL
万方数据
维普
