J Cancer 2020; 11(20):6059-6069. doi:10.7150/jca.44375 This issue

Research Paper

Demethylzeylasteral inhibits cell proliferation and enhances cell chemosensitivity to 5-fluorouracil in Colorectal Cancer cells

Yang Yang1*, Jing Han2*, Yanlin Ma3, Jianfeng Zhang1, Zhenya Zhang1✉, Guiying Wang4,3✉

1. Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
2. Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
3. The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
4. The Third Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
*These authors contribute equally in this work.

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Citation:
Yang Y, Han J, Ma Y, Zhang J, Zhang Z, Wang G. Demethylzeylasteral inhibits cell proliferation and enhances cell chemosensitivity to 5-fluorouracil in Colorectal Cancer cells. J Cancer 2020; 11(20):6059-6069. doi:10.7150/jca.44375. Available from https://www.jcancer.org/v11p6059.htm

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Abstract

Malignant growth and chemotherapy resistance to 5-fluorouracil (5-FU) are the obstacles to the treatment of Colorectal cancer (CRC). There is need to develop effective therapeutic option. Demethylzeylasteral benefits to immune and anti-tumor function. However, the role demethylzeylasteral played in colorectal cancer remains unclear. Here, our study confirmed that demethylzeylasteral could inhibit the cell malignant capacity, such as proliferation, migration and invasion. And we also found demethylzeylasteral could cause cell cycle arrest and apoptosis. Followed we verified that combination demethylzeylasteral with 5-FU has a better curative effect in vitro. The two drugs function synergistically in SW480 and additionally in RKO. IC50 values of 5-FU decreased when combined with demethylzeylasteral. Next, we used the network pharmacology approach to explore the the potential molecular mechanism of demethylzeylasteral. We constructed the “Colorectal - targets - Demethylzeylasteral” and protein-protein interactions (PPI) networks. And 15 hub genes were found in PPI network. Then Gene Ontology (GO) enrichment analysis showed that demethylzeylasteral may affect cell cycle, apoptosis, invasion and response to chemotherapy drugs. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated demethylzeylasteral may be involved in many cancer-related pathways. Taken together, the network pharmacology approach provided a potential mechanism of demethylzeylasteral in colorectal cells. Our study indicated that demethylzeylasteral could exert anti-tumor effects and enhance the sensitivity of the Colorectal cells to 5-FU, suggesting a promising ability to serve as an anti-cancer agent in Colorectal cancer.

Keywords: Colorectal, Demethylzeylasteral, 5-Fluorouracil, Chemosensitivity