The results demonstrated that ECT increased radiation response of cells and tumors, and that the predominant underlying mechanism was increased cisplatin accumulation in the cells of tumors [ 20- 22].
Survival curves generated using the clonogenic assay showed increased radiation-induced cell death with the combined treatment of olaparib and PI-103 in both MDA-MB-435S and MDA-MB-231-BR cells.
Exposure of cells either to BLM, electroporation or ECT statistically significantly increased radiation response of LPB cells.
Although previous studies demonstrated significantly increased radiation sensitivity of tumor cells in vivo[ 4] and in vitro[ 33] in the presence of 17-DMAG, the radiosensitivity of normal fibroblasts was not altered by Hsp90 inhibition [ 34], suggesting that the radiosensitization induced by 17-DMAG is tumor-specific.
These results suggest a strong correlation between the attenuation of G2/M arrest and the increased radiation sensitivity in MCF-7 cells treated with IR in the presence of Rac1 inhibition.
The PTEN-overexpressing Hek293 cells clearly showed increased radiation resistance compared with the empty vector control.
Likewise, siRNA targeting of YB-1 increased radiation sensitivity tested in MDA-MB-231 cells.
To confirm that anti-VEGF or anti-VEGFR2 increased radiation-induced endothelial cell apoptosis in vivo, MCA/129 tumors were excised at 4 6 h post-irradiation and co-stained with an antibody to the endothelial selective cell surface marker CD34 (blue in Figure S12) and TUNEL for apoptosis (brown), as described[6].
We have previously reported increased radiation-induced intestinal epithelial cell apoptosis and epithelial barrier dysfunction in response to LPS challenge that resulted in translocation of commensal bacteria in GC-C−/− mice [ 16, 17].
Depletion of endogenous INPP4B synergistically increased radiation-induced RR-HEp-2 cell death from 16% (radiation alone) to 28% (radiation plus INPP4B knockdown), as determined by a flow cytometry analysis (Fig. 4D, left), results that were confirmed by observation of cell morphology (Fig. 4D, middle).
