Oncology Letters
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2017
·Vol. 15
·期 3
·3192-3196
·
IF 1.39
Meng Zhou,Youli Zhang,Hong Wei,Junbo He,Dawei Wang,Baoding Chen,Jian Zeng,Aihua Gong,Min Xu
Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit‑8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial‑mesenchymal transition (EMT) and the Hippo‑yes‑associated protein (YAP) pathway were detected using western blot analysis. It was revealed that D6R significantly inhibited the proliferation, migration and invasion abilities of SW1990 and PaTu8988 cells. Additionally, D6R led to the upregulation of E‑cadherin (an epithelial marker), and the downregulation of N‑cadherin and vimentin (mesenchymal markers) in SW1990 and PaTu8988 cells. Furthermore, the results of the present study revealed that D6R significantly affected the YAP phosphorylation level and the total YAP protein level, indicating that D6R was functionally involved in the Hippo‑YAP signaling pathway. It has been suggested that D6R‑suppressed EMT in SW1990 and PaTu8988 cells may occur via the Hippo‑YAP pathway and that it may be a feasible drug to ameliorate the malignant phenotype of SW1990 and PaTu8988 cells.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biology-Basel
·
2026
·Vol. 15
·期 10
·788
·
IF 4.3
Xiaolong Zhou,Mihan Wu,Han Wang,Xiangchen Li,Songbai Yang,Ayong Zhao
Simple SummaryThis study investigated the anticancer properties of goose blood by treating SW1990 cancer cells with goose serum and plasma. Results showed that both treatments significantly inhibited cancer cell proliferation and viability, successfully inducing apoptosis. Transcriptome analysis revealed this suppression was driven by the regulation of genes involved in key pathways, including lipid metabolism, JAK-STAT signaling, and IL-17 signaling. In addition, metabolomic comparisons between goose and chicken blood identified unique bioactive substances in goose blood, such as cucurbitacin D, which likely contribute to halting cancer migration.Goose blood has anticancer properties and was recorded in ancient China, but the specific molecular mechanisms underlying this effect still require further exploration. In this study, SW1990 cells were treated with goose serum or plasma, and transcriptome analysis was performed to explore the function of goose blood on cancer cells. Metabolomic profiling was also performed on goose serum, goose plasma, chicken serum, and chicken plasma to identify the bioactive substances responsible for the anticancer effect. The study examined the effects of goose plasma and serum on SW1990 cells and compared the metabolites between goose and chicken blood. Wound scratch, CCK-8, and Annexin V-PI assays showed that goose plasma and serum inhibited SW1990 cell proliferation at 24 and 48 h. Both treatments reduced cell viability, with serum inducing early and late apoptosis and plasma inducing late apoptosis. RNA sequencing (RNA-seq) identified 2259 (1418 upregulated, 841 downregulated) and 2731 (1844 upregulated, 887 downregulated) differentially expressed genes (DEGs) in the plasma and serum groups versus the negative control (NC), respectively, and 689 DEGs between the plasma and serum groups. Gene Ontology (GO) and KEGG pathway analyses revealed that the DEGs were enriched in processes such as lipid metabolism, JAK-STAT, and IL-17 pathways. Untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis identified distinct metabolites in goose and chicken blood, with unique metabolites and differential ones between groups. In SW1990 cells, four metabolite subclusters matched the plasma and serum effects. In summary, goose blood can suppress cancer cells by regulating gene expression to affect the key signaling pathways involved in cancer cell apoptosis and autophagy. Certain metabolites present at high concentrations in goose blood, such as cucurbitacin D and Oleoyl-L-carnitine, may also contribute to the inhibition of cancer cell proliferation and migration. These findings suggest that goose blood holds broad application prospects as a future auxiliary drug for cancer treatment, and this study provides a theoretical basis for the further application of goose products.
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Weiqi Cui,Junwei Zhang,Deqiao Wu,Jingxian Zhang,Hui Zhou,Ying Rong,Fanglin Liu,Bo Wei,Xia Xu
Background Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Ponicidin, a tetracyclic diterpenoid active ingredient extracted from the traditional phytomedicine Rubescens, has high safety and great inhibitory effect on the proliferation of a variety of cancer cells, especially malignant tumor cells of the digestive tract. However, the inhibitory effect and mechanism of ponicidin on pancreatic cancer cells is still unclear. Our study aimed to use metabonomics technology to analyze and explore the suppressive effect of ponidicin against pancreatic cancer cells. Methods MTT and flow cytometry were conducted to study the potential effect of ponicidin on SW1990 cells. Secondly, UPLC-MS/MS was used to analyze the small molecule metabolites and relevant differential metabolic pathways induced by ponicidin treatment. Furthermore, through the determination of glutathione peroxidase 4 (GPX4) activity and molecular docking simulation experiments, the effects of intracellular GPX4 activity and GSH/GSSG ratio after ponicidin were evaluated. Finally, the determination of the content of iron ions and malondialdehyde in cells, and the experiment of the effect of ferroptosis inhibitors on cell viability, the effect of ponicidin on the induction of ferroptosis in SW1990 cells was also detected. Results The IC 50 of ponicidin on SW1990 cells was 20 μM, which could significantly induce cell apoptosis and arrest the cells in G 2 /M phase. Metabolomics results showed that the contents of endogenous small molecules such as gamma-glutamylcysteine, 5-oxoproline, glutamic acid, reduced glutathione (GSH), oxidized glutathione (GSSG) and arachidonic acid have changed significantly. Main differential compounds were involved in the gamma-glutamyl cycle and polyunsaturated fatty acid metabolism of pancreatic cancer cell lines. Additionally, ponicidin could covalently bind to GSH in SW1990 cells to form a conjugate Pon-GSH, which further reduced the content of free GSH and GPX4 activity in cells. Notably, ponicidin dose-dependently increased levels of iron ions, malondialdehyde and reactive oxygen species in SW1990 cells, and the ferroptosis inhibitors could significantly block the effects of ponicidin on the proliferation of SW1990 cells. Conclusion Ponicidin could suppress the pancreatic cancer cell proliferation via inducing ferroptosis by inhibiting the gamma-glutamyl cycle and regulating the polyunsaturated fatty acid metabolism in SW1990 cells.
研究领域:
肿瘤学
·
药理学
·
代谢组学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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