ABSTRACT
This study specifies the basic principles to selectively kill p53-deficient cells (H1299, FaDu) by taxol and to protect p53 wild type cells (A549) by the prior administration of structurally related flavonoids (apigenin, genistein, and quercetin). Cytotoxic and cytostatic properties of flavonoids were investigated in vitro by flow cytometry and were compared to known anticancer drugs (cisplatin, doxorubicin, etoposide). It was confirmed that doxorubicin induced growth arrest and protected A549 cells from taxol while simultaneously killing or blocking H1299 and FaDu cancer cells. It was found that doxorubicin could be successfully substituted in this way by the isoflavone genistein used at physiologically relevant concentrations. The other compounds analyzed revealed less selectivity (apigenin, cisplatin) or demonstrated higher toxicity (cisplatin, etoposide, and quercetin). We concluded that genistein-based therapy may have antagonistic effects when combined with mitotic poisons. The proposed therapeutic strategy allows protection of p53 wild type cells from taxol and selectively increases apoptosis in p53-deficient cells. This strategy exploits the naturally occurring compound that can be used without significant toxicity in rather high concentrations as present in common diets.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Genistein/pharmacology , Lung Neoplasms/drug therapy , Paclitaxel/pharmacology , Tumor Suppressor Protein p53/physiology , Cell Cycle/drug effects , Cell Line, Tumor , Cisplatin/pharmacology , Dose-Response Relationship, Drug , Doxorubicin/pharmacology , Etoposide/pharmacology , Humans , Lung Neoplasms/pathologyABSTRACT
PURPOSE: The aim of our study was to develop a method for the fusion of images received after repeated staining of the same sample taking into account spatial differences between the images. MATERIAL AND METHODS: A method of objective fusion performance was investigated on the images receiving during multistep staining of the xenograft tumour cross-sections. RESULTS: It was shown that several images receiving from different steps of staining procedures may be successfully fused by fluorescent marking of slide position with Trout red blood cells before analysis. CONCLUSIONS: Proposed technique provides an accurate rigid fusion of light and fluorescent images receiving during multistep image analysis under microscope and may be applied for study of neovascularisation.
