Baicalin suppresses colorectal cancer cell proliferation, potentially via ARRDC4: Bioinformatics and experimental analysis

Colorectal cancer (CRC) is a malignant digestive tumor mostly prevalent among adolescents and has great proliferation potential. Baicalin is a flavonoid derived from the dried root of Scutellaria baicalensis, it has tumor-suppressing effects on various kinds of tumors. Although baicalin has been shown to regulate genes associated with CRC, its role in cancer proliferation remains poorly illustrated. In this work, we evaluated the effect of baicalin on the proliferative ability of three CRC cell lines using a cell counting kit-8 assay. Furthermore, we screened for differentially expressed genes in HCT-116 cells using baicalin-treated samples and control samples on a gene expression profile microarray. We identified 19 genes were identified significantly downregulated by baicalin, which may potentially play an indispensable role in the proliferation of HCT-116 cells. High-content screening evaluated whether silencing the 19 genes affected HCT-116 cell growth. The results showed that knocking down ARRDC4 exhibited the most potent inhibition of cell proliferation. ARRDC4 expression was knocked down by transfecting CRC cells with lentiviral shRNA. MTT assay, Caspase-Glo 3/7 assay and immunohistochemistry analysis were performed to explore the effects of baicalin on proliferation and apoptosis of CRC cells. Besides, RT-PCR showed that the expression levels of ARRDC4 mRNA decreased significantly in HCT-116 cells after baicalin treatment. In conclusion, these findings indicated that baicalin may attenuated the expression of ARRDC4 via regulating the levels of LCN2, Claudin-2 and GSTA4 to inhibit HCT-116 cell proliferation. The theoretical underpinnings for the investigation of the pharmacological effects of baicalin in the treatment of human CRC were also established in this study. & COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).