Deoxyschizandrin Inhibits the Proliferation, Migration, and Invasion of Bladder Cancer Cells through ALOX5 Regulating PI3K-AKT Signaling Pathway

Abstract

Objective. Deoxyschizandrin has a significant inhibitory effect on a variety of tumor cells. However, the effect of Deoxyschizandrin on bladder cancer cells and its mechanism are still unclear. Methods. Bladder cancer cells were treated with different concentrations of Deoxyschizandrin for 24 h, 48 h, and 72 h. The inhibition rate of cell proliferation was detected by CCK-8 assay. The changes of cell migration and invasion were detected by wound healing and Transwell assay. Based on the structure of Deoxyschizandrin, the protein targets of Deoxyschizandrin were predicted by bioinformatics database and verified by RNA and protein. Then, the expressions of ALOX5 and PI3K-AKT signaling pathway proteins were detected by Western blot in bladder cancer cells treated with Deoxyschizandrin. Result. Deoxyschizandrin inhibited the proliferation, migration, and invasion of bladder cancer cells in a time- and concentration-dependent manner. Bioinformatics analysis showed that Deoxyschizandrin had 100 protein targets; among them, the score of ALOX5 was the highest, and the mRNA and protein levels of ALOX5 decreased after treatment with different concentrations of Deoxyschizandrin. Western blot results showed that compared with the control group, Deoxyschizandrin could significantly reduce the expression of p-PI3K and p-AKT, and overexpression of ALOX5 could significantly enhance the expression of p-PI3K and p-AKT. Compared with Deoxyschizandrin or overexpression of ALOX5, the expression of p-PI3K and p-AKT of Deoxyschizandrin combined with overexpression of ALOX5 recovered. Conclusion. Deoxyschizandrin inhibits the proliferation, migration, and invasion of bladder cancer cells through ALOX5 regulating PI3K-AKT signaling pathway.

Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo

“…Indeed, our results provide evidence for a more intensive autophagy present in cells treated with 2. A novel study of Chi et al indicates that the downregulation of 5-Lipoxygenase via the PI3K/Akt signaling pathway results in the reduced proliferation and migration of tumor cells, confirming, once again, the importance of this enzyme in tumor treatment [43]. Nevertheless, one should have in mind that the inhibition of solely 5-LO could result in the intracellular accumulation of prostaglandins [44], raising a need for more detailed investigation of pharmacological effects in future research.…”

Integrated microbiome, metabolome and transcriptome profiling reveals the beneficial effects of fish oil and Bacillus subtilis jzxj-7 on mouse gut ecosystem

“…62 The PI3K–Akt signaling is activated by phosphorylation, and regulates cell proliferation, differentiation and apoptosis. 63 Activation of PI3K–Akt signaling protects cells from injury and inhibits cell apoptosis under oxidative stress, whereas inhibition of Akt activation makes cells more sensitive to oxidative stress and vulnerable to injury. 64 The PI3K–Akt signal pathway plays a vital role in several antioxidant reactions and inflammatory cascades.…”

JQ1 inhibits the proliferation of thyroid cancer TPC-1 cells by regulating the ferroptosis genes ALOX5 and GDF15

“…It has been reported that ALOX5 can promote tumour cell growth through the PI3K/AKT pathway and MAPK pathway [54,74], while GDF15 can act through the PI3/Akt pathway and TGFβ/SMAD pathway to promote tumour growth [75,76]. Therefore, in the functional study of ALOX5 and GDF15, we used the GO and KEGG databases and found by enrichment analysis that the main functions of the ALOX5 and GDF15 genes were related to lipid metabolism, the cell signalling pathway, arachidonic acid metabolism, the MAPK signalling pathway and the IL-17 signalling pathway by enrichment analysis.…”