Mechanistic study on ursolic acid inhibiting the growth of colorectal cancer cells through the downregulation of TGF-β3 by miR-140-5p.

Autor: Zhang T; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Xiang F; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Li X; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Chen Z; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Wang J; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Guo J; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Zhu S; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Zhou J; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Kang X; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China., Wu R; Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2024 Jan; Vol. 38 (1), pp. e23581. Date of Electronic Publication: 2023 Dec 03.
DOI: 10.1002/jbt.23581
Abstrakt: Colorectal cancer (CRC) is a common digestive tract tumor with a high incidence and a poor prognosis. Traditional chemotherapy drugs are usually accompanied by unpleasant side effects, highlighting the importance of exploring new adjunctive drugs. In this study, we aimed to explore the role of ursolic acid (UA) in CRC cells. Specifically, HT-29 cells were treated with UA at different concentrations (10, 20, 30, and 40 μM), and the expression of miR-140-5p, tumor growth factor-β3 (TGF-β3), β-catenin, and cyclin D1 was determined by real-time quantitative PCR. The cell cycle and apoptosis were checked by flow cytometry, and cell proliferation was detected by Cell Counting Kit-8 assay. The HT-29 cell model was established through overexpression (miR-140-5p mimics) and interference (miR-140-5p inhibitor) of miR-140-5p. Western blot was used to detect the protein expression of TGF-β3. We found that UA could inhibit the proliferation of HT-29 cells, block cells in the G 1 phase, and promote cell apoptosis. After UA treatment, the expression of miR-140-5p increased and TGF-β3 decreased. Notably, miR-140-5p downregulated the expression of TGF-β3, while the overexpression of miR-140-5p exerted a similar function to UA in HT-29 cells. Additionally, the messenger RNA expression of TGF-β3, β-catenin, and cyclin D1 was decreased in HT-29 cells after UA treatment. In conclusion, UA inhibited CRC cell proliferation and cell cycle and promoted apoptosis by regulating the miR-140-5p/TGF-β3 axis, which may be related to the inhibition of Wnt/β-catenin signaling pathway.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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