| Objective: Tumor is a kind of lethal disease. Glioma, also called as high-grade glioma is the highest frequency among brain-malignant tumors. The first cure method is the exairesis.Due to the wide availability of birth control methods and because of our success in treating other diseases such as infections and cardiovascular disease. The conventional therapy of solid tumour involves the use of surgery, radiotherapy and chemotherapy. Nowadays, approximately 70% of cancer patients are treated with radiotherapy and chemotherapy. However, for most common tumours, there has been little change in overall cure rates for over 40 years. The major obstacle impeding the success of radio-and chemo-therapy is that tumour cells show intrinsically or acquire resistance to irradiation or anticancer drugs.In order to increase tumour's sensitivity to irradiation in 1963, Adams pioneered a concept of the efficiency of radiosensitisation that was directly related to electron affinity of compounds, Then a number of radiosensitizers were synthesized and some of them have reached to the stage of clinical evalution. Moreover, as a branch of antineoplastic agents, cancer sensitizer has been beyonded the original concept of radiosensitizer, chemical agents that mimiced oxygen and directly and preferentially sensitized the resistant hypoxic tumour cell population to radiation, Today more and more cancer sensilizers are developed and effectively overcome a certain cause of resistance.In this thesis, we investigated the radiosensitisation of CpG ODN107, and it's possible molecular mechanisms in order to search for high efficacy and low toxicity sensitizer.Methods: CHG-5 were exposed to CpG ODN107 at different concentrations (1, 3, 10, 30μg/ml) or/andβ-ray irradiation (5 Gy),①the viability of were measured by MTT method;②the ability of colony formation and migration of CHG-5 cells were observed by colony formation test and scratch method;③the TNF-α,IL-12 and INF-γsecretion from CHG-5 cells were detected by ELISA method;④AP-1 activation within CHG-5 cells was observed using electrophoretic mobility shift assay (EMSA);⑤NO level was tested by Griess method;⑥To establish athymic mouse tumor implant models using CHG-5 cells, the hibition of CpG ODN107 andβ-ray irradiation on the tumor growth were observed。Results:①CpG ODN107 inhibited the viability of CHG-5 cells in a dose dependent manner, and the inhibitory effect was enhanced when CpG ODN107 (10μg/ml) were combined withβ-ray irradiation;②CpG ODN107 (10μg/ml) could inhibit the colony formation and migration of CHG-5 cells;③CpG ODN107 (10μg/ml) could increase TNF-α,IL-12 and INF-γsecretion, and its ability was enhanced when combined withβ-ray irradiation;④CpG ODN107 combined withβ-ray irradiation inhibited the AP-1 activation within CHG-5 cells;⑤CpG ODN107 combined withβ-ray irradiation increased NO level in CHG-5 cells;⑥CpG ODN107 combined withβ-ray irradiation apparently decreased the growth of the CHG-5 glioma xenografts in nude mice.Conclusion: Our results demonstrated that CpG ODN107 can increase the radiosensitivity of human glioma CHG-5 cells line and apparently decreased the growth of the CHG-5 glioma xenografts in nude mice, which may be tightly related to increasing secretions of IL-12, IFN-γ, TNF-αand NO from cells and the inhibition AP-1 activation.
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