期刊
PHYTOMEDICINE
卷 98, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2022.153972
关键词
Scutellarin; Colorectal cancer; Colitis-associated colorectal cancer; Hedgehog signaling pathway; NF-kappa B signaling pathway; RNA-seq
资金
- National Natural Science Foundation of China [81573813, 81173598]
- Sichuan Provincial Administration of Traditional Chinese Medicine of China [2021MS447]
- Excellent Talent Program of Chengdu University of Traditional Chinese Medicine of China [GJJJ2021003]
- Health Commission of Sichuan Province of China [21PJ107]
Scutellarin effectively ameliorates colitis-associated colorectal cancer (CAC) by suppressing Hedgehog signaling pathway activity, showing potential clinical application.
Background: Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) and mainly develops from long-term intestinal inflammation. Mounting evidence reveals that activated Hedgehog signaling pathway plays a vital role in the pathogenesis of CRC. Scutellarin is a type of phytochemical flavonoid with a powerful efficacy on various malignancies, including CRC.& nbsp;Aim: Here, we studied the therapeutic effect of scutellarin on CRC and its direct regulating targets.& nbsp;Methods: The CAC model in mice was established by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by detection of the efficacies of scutellarin on the carcinogenesis, apoptosis, inflammation, Hedgehog signaling cascade and complicated inflammatory networks in CAC tissues of mice. In CRC SW480 cells, the effects of scutellarin on malignant phenotype, apoptosis and Hedgehog signaling were examined. In TNF-alpha-stimulated IEC-6 intestinal epithelial cells, the actions of scutellarin on inflammatory response and Hedgehog signals were assessed as well.& nbsp;Results: Scutellarin significantly ameliorated AOM/DSS-caused CAC in mice and induced apoptosis in CAC tissues of mice, by inhibiting NF-kappa B (nuclear factor kappa B) -mediated inflammation and Hedgehog signaling axis. RNA-seq and transcriptome analysis indicated that scutellarin regulated complicated inflammatory networks in mouse CAC. Also, scutellarin suppressed the proliferation, migration, colony formation, and induced apoptosis of SW480 cells by down-regulation of Hedgehog signaling pathway activity. Additionally, scutellarin lessened NF kappa B-mediated inflammatory response in TNF-alpha-stimulated IEC-6 cells, by attenuating Hedgehog signaling cascade.& nbsp;Conclusion: Scutellarin potently ameliorates CAC by suppressing Hedgehog signaling pathway activity, underpinning the promising application of scutellarin to CRC in clinical settings.
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