English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Combination therapy is considered a promising therapeutic modality in enhancingtreatment efficacy. The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathwayis almost universally dysregulated in breast cancer, with specific occurrenceof PTEN mutations; thus, it has become an attractive target for cancer treatment.However, the use of single targeted therapeutics against the PI3K/AKT pathwayhas demonstrated only modest clinical benefits. In this study, recombinant adenovirus-mediatedgene transfer of PTEN (AD-PTEN) combined with treatment with LY294002 was utilizedto evaluate the effects of suppression of breast cancer cell proliferation. Herein,we show that AD-PTEN significantly enhanced the sensitization of breast cancercells to LY294002. The 50% inhibitory concentration (IC50) values of LY294002were significantly decreased to a greater extent in cells transfected with combinationtherapy. In addition, treatment of AD-PTEN-transfected cells with LY294002 resultedin significantly reduced cell viability and invasion ability compared to singleLY294002 treatment. Using western blotting, we found that combination treatmentresulted in lower levels of phosphorylated AKTSer473 and GSK-3βSer9 than singletreatment with LY294002. Furthermore, we showed a significant decrease in nuclearβ-catenin, Fra-1, Tcf-4 and c-Myc by combination treatment. Our results indicatethat AD-PTEN sensitization of breast cancer to LY294002 is achieved by increasedGSK-3β activity, thus resulting in inhibition of the β-catenin signaling pathway.

PTEN activation sensitizes breast cancer to PI3-kinase inhibitor through the β-catenin signaling pathway