The Radiation Sensitizing Enhancement Effiect Of G2/M Checkpoint Abrogators In Human Esophageal Carcinoma Cell Line

Esophageal cancer is the common disease in our country, which affects thepublic health. Currently the recommended therapy of curing this cancer is thecombination of radiation, chemotherapy and operation. To enhance theradiosensitivity of the cancer cell is one of the most important ways to improve theeffects of radiotherapy. The irradiation can cause the G2phase arrest, offering enoughtime for the DNA damage repairing. However,the G2checkpoint abrogators canpromote the cancer cells with DNA damage into the mitotic phase, which causes themitotic catastrophe and cell death. And we study the cell cycle arrest(especially G2phase) of the esophageal cancer cells TE-5treated with G2checkpiont abrogatorsafter X-ray, clarify whether the drugs can enhance the radiosensitivity, and discuss thepossible mechanism and clinical significance.Flow cytometry are applied to test the cell cycle arrest of the TE-5squamous cellcarcinoma lines treated with G2checkpoint abrogators(caffeine；Pentoxifylline；Lisofylline；UCN-01；Hymenialdisine；SB-218078；Isogranutimide；Go6976) inresponse to X-ray,and observe the results of X-ray induced G2arrest. And the MTTassays are applied to test the cytotoxicity of the drugs, then the trypan blue dyeexclusion assays are used to test the TE-5cell viability and radiosensitivity. Theexpression of G2phase were detected through the Western Blot.Results: Flow cytometry: the X-ray can induce TE-5cells G2arrest in adose-dependent manner. Meanwhile different G2checkpoint abrogators shows littleeffect on the distributions of cell cycle,but can abrogate the X-ray induced G2arrest,with a dose-dependent manner of drugs. The MTT assay results show that thecytotoxicity of G2checkpoint abrogators increase in a dose-dependent mannerfollowing a48-hour treatment. And trypan blue exclusion assay shows that the drugscan decrese the TE-5cells' survival percent following X-ray treatment, with UCN-01'synergetic effect most significant(P＜0.05). The Western Blot results showed thatUCN-01can decrease the CyclinB1's expression level of TE-5cells treated with X-ray.Conlusion: G2checkpoint abrogators,expecially UCN-01,can enhance theradiosensitivity of TE-5cells. The mechanism may be that UCN-01abrogates X-rayinduced G2arrest. And this offers a new evidence and guidence for the therapy ofesophageal cancer.