Chloropyramine Hydrochloride

Drug-loaded poly(lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a mold-less technique to investigate whether the combined delivery of both Y15 (FAK inhibitor) and metformin would result in enhanced effects on cell viability compared to the release of each drug alone for the treatment of platinum-resistant ovarian cancer (PROC).

Scaffolds were fabricated using an easy and economical mold-less technique that combined PLGA and the drugs (i.e. metformin and/or Y15) in tetraglycol and injected in PBS, to form a globular morphology.

The exposure of cells to metformin and Y15 resulted in a significantly enhanced cytotoxic efficacy compared to single-drug treatment with either metformin or Y15. When the drugs were delivered using the PLGA scaffolds, the combination of the two drugs was significantly more cytotoxic compared to scaffolds containing metformin only and Y15 only.

The combination of metformin and Y15 can result in an increase in antitumor activity in PROC cells through apoptosis. The delivery of both drugs from the PLGA biomaterial scaffold allowed for a more enhanced combinational effect compared to the utilization of free drugs (without a scaffold) and should be further explored as a promising treatment of PROC.

Overexpression of PTN (Pleiotrophin) in breast cancer cells stimulates breast cell proliferation and anti-apoptosis via the FAK/Src signaling pathway.1,2,4,5-Benzenetetramine tetrahydrochloride (C₆H₁₄Cl₄N₄) known as Y15 is an inhibitor that specifically blocks phosphorylation of Y397-FAK and total FAK phosphorylation. The exogenous PTN protein was induced to be expressed by a prokaryotic expression strain. The addition of PTN protein decreased the sensitivity of breast cancer cells to Y15, as shown by both MTT and flow cytometry assays. Breast cancer cells transfected with sh-RNA knockdown PTN were analyzed by real-time fluorescence quantitative PCR reaction (RT-PCR) and protein immunoblotting 24 h after transfection. MTT assay data showed a significant increase in the IC50 value of Y15 against breast cancer cells in the presence of PTN protein. Flow cytometry data confirmed the dose-dependent anti-apoptotic effect of PTN protein in Y15-treated breast cancer cells. After transfection with sh-RNA, Y15 further inhibited the FAK pathway, greatly reducing cell survival and promoting apoptosis. Western blotting analysis showed that knockdown of PTN protein with sh-RNA resulted in increased apoptosis and elevated levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3 in Y15-induced breast cancer cells. Finally, it was hypothesized that PTN and Y15 were associated with a significant increase in the IC50 value of PTN and Y15 in breast cancer cells by western blotting analysis. It was hypothesized that PTN and Y15 regulate the proliferation and apoptosis of breast cancer cells through the AKT/PI3K pathway. The results demonstrated that PTN affects the sensitivity of the kinase inhibitor Y15, and PTN silencing and Y15 may inhibit the survival of breast cancer cells through the AKT/PI3K pathway, which lays the foundation for subsequent in-depth research on the clinical treatment of breast cancer.