Document Type
Article
Publication Date
6-19-2023
Abstract
Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and normal human colon epithelial cells. In vivo animal models were used to document the antitumor activity of HQ and baicalin. The mechanism of growth inhibitory activity of HQ is due to inhibition of proliferative signaling pathways including the CDK-RB pathway. In addition, HQ enhanced the antitumor effects of 5-FU and capecitabine in vivo. Furthermore, we identified baicalin as an active component of HQ. The combination of baicalin and 5-FU demonstrated synergistic activity against 5-FU-resistant RKO-R10 cells. The combination significantly inhibited in vivo tumor growth greater than each treatment alone. RPPA results showed that the signaling pathway alterations in CRC cells were similar following HQ and baicalin treatment. Together, these results indicate that HQ and its component baicalin enhance the effect of 5-fluorouracil-based chemotherapy via inhibition of CDK-RB pathway. These findings may provide the rational basis for developing agents that can overcome the development of cellular drug resistance.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Liu, Haizhou; Liu, Hui; Zhou, Zhiyi; Chung, Jessica; Zhang, Guojing; Chang, Jin; Parise, Robert A; Chu, Edward; and Schmitz, John C, "Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy via Inhibition of Proliferative Signaling Pathways" (2023). Abington Jefferson Health Papers. Paper 84.
https://jdc.jefferson.edu/abingtonfp/84
PubMed ID
37337282
Language
English
Comments
This article is the author's final published version in Cell Communication and Signaling, Volume 21, Issue 1, 2023, Article number 147.
The published version is available at https://doi.org/10.1186/s12964-023-01156-7.
Copyright © The Author(s) 2023.
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