Dataset Information

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

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.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7477418 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Yang Yang Y Han Jing J Ma Yanlin Y Zhang Jianfeng J Zhang Zhenya Z Wang Guiying G

Journal of Cancer 20200819 20

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 demeth ...[more]

PMID: 32922546

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Project description:Signal transducer and activator of transcription 3 (STAT3), a transcriptional factor involved in tumorigenesis and cancer stemness formation, contributes to drug resistance in cancer therapies. STAT3 not only mediates gene transcription but also participates in microRNA suppression. This study identified a STAT3-downstream micro RNA (miRNA) involved in drug resistance against regorafenib in colorectal cancer stem-like tumorspheres. Small RNAseq was used to investigate differential microRNAs in colorectal cancer cell-derived tumorspheres and in a STAT3-knockdown strain. The miRNA-mediated genes were identified by comparing RNAseq data with gene targets predicted using TargetScan. Assays for detecting cell viability and apoptosis were used to validate findings. The formation of colorectal cancer stem-like tumorspheres was inhibited by BBI608, a STAT3 inhibitor, but not by regorafenib. Additional investigations for microRNA expression demonstrated an increase in 10 miRNAs and a decrease in 13 miRNAs in HT29-derived tumorspheres. A comparison of small RNAseq results between tumorspheres and HT29shSTAT3 cells revealed the presence of four STAT3-mediated miRNAs in HT29-derived tumorspheres: hsa-miR-215-5p, hsa-miR-4521, and hsa-miR-215-3p were upregulated, whereas miR-30a-5p was downregulated. Furthermore, hsa-miR-4521 was associated with poor overall survival probability, and miR-30a-5p was associated with better overall survival probability in patients with rectum cancer. Comparisons of RNAseq findings between HCT116- and HT29-derived tumorspheres revealed that HSPA5 were mediated by the STAT3-miR-30a-5p axis, which is overexpressed in colorectal tumorspheres associating to anti-apoptosis. In addition, the transfection of miR-30a-5p and inhibition of HSPA5 by HA15 significantly reduced cell viability and increased apoptosis in HT29 cells. In conclusion, a STAT3-miR-30a-5p-HSPA5 axis was observed against regorafenib-mediated apoptosis in colorectal cancer tumorspheres. The expression of miR-30a-5p was repressed by STAT3; in addition, HSPA5 was identified as the target gene of miR-30a-5p and contributed to both tumorsphere formation and anti-apoptosis.

Dataset Information

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

Publications

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

Similar Datasets

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