| Objective:Radiotherapy constitutes a major part of the treatment of cancer patients. Of all cancer patients, 70% receives radiotherapy. All cancer cells can be killed theoretically with enough doses, with are hampered by the limited endurance of normal tissue. With the limited treat doses, seaking for any methods that can be increase the tumor cells sensitivity to irradiated injury become more important. Chronobiology has indicated that the periodicity in cellular proliferation or metabolic activity ususally retained both in normal and tumor tissues. It has been proved that chronotherapy can improve cancer treatment, meanwhile decrease the side effect a lot .The present study was designed to investigate the role of one key clock gene- Per2, effect on sensitivity to 60Co-γray irradiation. First, We concluded the effects of PER2 overexpression in Lewis lung cancer cells (LLCs) and mouse mammary carcinoma cells( EMT6 ) on cell growth and DNA injury afterγray irradiation. Then based on above results, we choiced the different time of mPer2 rhythmic expression both in cultured LLC cells and in transplanted tumor , treated by 60Co-γray irradiation , and observe the degree of tumor cell growth depression and the side effects on mice within the circadian cycle in vitro and in vivo, Finally, we apply the methods of molecular biology, cytobiology and chronobilogy to detect the mPer2 effect on its down regulated CCGs, such as genes involved in cell proliferation, DNA injury and repair, and apoptosis etc. Then elucidate the mechanism of mPer2 influence the sensitivity of tumor cell toγray. We believe that radiochronotherapy appear to offer a new way to improved cancer treatment.Method:1. Lipofectamine-mediated gene transfection method was used to transfer...
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