Accor dingly, the mean EGFR and VEGFR 2 TKI ZD6474 Inhibitors,Modulators,Libraries may be an effective tool in inhibiting tumor formation as well as blocking breast cancer invasion and potentially metastasis. Additionally, there was an increase in E cadherin expres sion in MCF 7 and MDA MB 468 cells after treatment with either ZD6474 or UV B, suggesting a role in cytoskeletal reorganization and stabilization, but the decrease in expression of E cadherin in combination treatment may be a conse quence of induction of apoptosis. Next we investigated the role of ZD6474 and or UV B radiation in the pro duction of VEGF, proangiogenic factor, responsible for migration and invasion of breast cancer cells. VEGF se cretion in the serum free culture conditioned medium was measured using ELISA after 48 h post treatment of breast cancer cells with ZD6474 and or UV B radi ation.
It was found that ZD6474 inhibits VEGF secre tion by 6 fold as compared to untreated MCF 7. Though there was upregulation of VEGF secretion in MCF 7 irradiated UV B, but the change was not significant. It was found that ZD6474 inhibited VEGF Inhibitors,Modulators,Libraries secretion significantly in UV B irradiated MCF 7 as compared untreated MCF 7. There is also decrease in secretion of VEGF in ZD6474 Inhibitors,Modulators,Libraries treated MDA MB 468 as compared to un treated cells, and the decrease is also signifi cant in combined ZD6474 UV B treated MDA MB 468 cells. ZD6474 in combination with UV B induces cytoskeleton reorganization in breast cancer cells To understand and correlate the effects of ZD6474 and or UV B in cell migration and motile phenotypes, we used confocal laser scanning microscopy to study cytoskeletal remodeling and generation of mem brane protrusions, such as pseudopodium, filipodia and ruffle formation.
ZD6474 lead to reorganization of F actin structure. Long stressed F actin filaments Inhibitors,Modulators,Libraries were ob served across the cell in ZD6474 as compared to control cells. Stress fibers were not prominently vis ible in UV B treated cells as compared to ZD6474. In contrast, the combination of ZD6474 and UV B pro duced F actin rings exclusively Inhibitors,Modulators,Libraries in the perinuclear zone and the contraction of cytoplasm, indicating apoptosis was noticeable. ZD6474 and UV B blocked membrane protrusions, such as microspikes, filopodia and lamelli podia formation, which was almost absent in MCF 7 and MDA MB 468 following combination treatment with ZD6474 and UV B.
The loss and dra matic collapse of cytoskelatal structure following com bination treatment may be a consequence of induction of apoptosis. In the study of cancer therapy and invasion, high resolution SEM is a vital tool for analysis of expres sion of microspikes like lamellipodia and fillipodia, a cytoskeleton protein involved in the movement of cancer cells. The ultra sellckchem structure of cells was observed by FE SEM. The images of untreated control MCF 7 and MDA MB 468 showed the appearance of lamellipodia and fillipodia in consistent with previous re sults observed under CLSM.