Regulation of radiation-induced apoptosis targeting signal transduction factors

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To develop more efficient regimens for various malignant tumors the attention has focused on searching for substances to sensitize cell lethality of tumors by radiation. Inhibitors against anti-apoptosis and/or cellular Proliferation signal transductions are as good candidates for enhancers of radiation Sensitivity on human cancer calls This study examined whether siRNAs or chemical inhibitors targeting key factors (NBS1, XIAP, P13-K, MAPK, Akt and heat proteins) in DNA repair and survival Signal transductions for anti-apoptosis and/or cellular, proliferation after radiation enhance radiation induced apoptosis, Further, it was examined whether; heavy-ion bin effectively, induce apoptosis p53 independently. We analyzed radiation/heat sensitivity apoptosis with colony formation assay, Western blot, fluorescent immuno-cytochemistry, arid hoechst staining using wild-type p53 or mutated p53 gene-transfected human lung and tongue cancer cells. We showed siRNAs targeting NBS1 and XIAP enhanced radiation sensitivity more efficiently in mutated p53 cells than the wild-type p53 cell Furthermore, LY294002 (inhibitor of PI3-K) enhanced radiation/heat sensitivity and radiation/heat-induced apoptosis p53 independently. PD98059 (inhibitor of MEK) and-SB203580 (inhibitor of p38) enhanced heat sensitivity but not radiation Sensitivity, Heavy-ion beams induced p53 independent apoptosis. Our results suggest that these siRNAs, chemical inhibitors and heavy-ion beams might contribute to high curative efficiency in radiation/heat cancer therapy for malignant cancer leading to enhanced, p53 independent radiation/heat sensitivity.