PP2

To study the role of src kinase families in NB, we first studied the morphological response of NB cell lines to src family inhibitor PP2 treatment. NB cell lines (SH-SY5Y, IMR32, RT-BM-1, CHP134, NLF, LA-N-5) were cultured in 0.1, 1, and 10 lM of PP2. Representative results are shown in Fig. 1a. All cell lines showed morphological changes by becoming round-shaped and forming aggregated cell clusters. Particularly, IMR32 and RT-BM-1 cells showed drastic clustering followed by detachment of cells from the culture dish. The majority of the floating cells were however viable, as shown by Trypan blue assay (data not shown). These changes occurred as early as 3 h after treatment with 10 lM of PP2. Contrastly, human fibroblast cells did not show significant change after PP2 treatment, suggesting that the inhibition of src family kinases has minimum effect on non-transformed cells.

Recently, the results of a large body of preclinical studies and clinical trials suggest that targeting the EGFR could represent a significant contribution to cancer therapy. Tyrosine kinases show promise as new therapeutic targets, and a number of tyrosine kinase inhibitors are currently undergoing clinical evaluation as cancer therapies. However, relatively little is known regarding these targeting on cervical cancer. In this paper, we presented evidence that PP1, PP2, and PP3 targeted different tyrosine phosphorylation sites on EGFR and Src, which may help to explain their different efficacies on inhibition of cervical cancer cell proliferation.