ku-55933 and pifithrin

Low dose irradiation (LDIR) induces hormesis and adaptive response in organism and mammalian cell lines. Notably, LDIR generates distinct biological effects in cancer cells from normal cells, e.g., it may affect the growth of cancer cells via the activation of certain cell signaling pathway, which does not exist in normal cells. Therefore, LDIR is considered as a promising assistant method of clinical cancer therapy. In this study, we chose human colorectal adenocarcinoma cell line HT-29 as the experimental model, and investigated the differential biological effects between 250 mGy single dose LDIR and 250 mGy intermittent LDIR pretreatments in high dose irradiation (HDIR) radiotherapy and 5-fluorouracil (5-FU) based chemotherapy. Through the cell growth assays, we observed that 250 mGy intermittent LDIR pretreatment significantly increased the killing effect of both radiotherapy and chemotherapy. Western blotting results showed that intermittent LDIR pretreatment apparently activated the ATM/p53 (ataxia telangiectasia mutated, ATM) pathway in radiotherapy; it also activated ERK and p38MAPK pathways in chemotherapy. When we used chemical inhibitors to block the ATM/p53 or p38MAPK pathways, the intermittent LDIR induced cell growth inhibitions were reversed. However, blockage of ERK pathway could not affect the cell growth inhibiton in chemotherapy. Taken together, our findings evaluated the intermittent LDIR as a potential valuable method that can enhance the effectiveness of radiotherapy and chemotherapy, especially in the radio- or chemo-resistant tumor types.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Ataxia Telangiectasia Mutated Proteins; Benzothiazoles; Cell Proliferation; Chemoradiotherapy; Colorectal Neoplasms; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Fluorouracil; HT29 Cells; Humans; Imidazoles; MAP Kinase Signaling System; Morpholines; p38 Mitogen-Activated Protein Kinases; Pyridines; Pyrones; Radiation Dosage; Toluene; Tumor Suppressor Protein p53