Studies On Radiosensitivity Related Genes In Esophageal Squamous Cell Carcinoma

Esophageal cancer is the fourth most common malignancy in China and esophageal squamous cell carcinoma (ESCC) is the most prevalent type. Radiotherapy remains an useful modality in treating ESCC as well as surgery. However, radiotherapy could not benefit all patients for the lack of methods to select radiosensitivity patients to take optimal treatment. In pursuit of candidate radiosensitivity genes in ESCC, we focused on cell cycle related genes and NF-κB in ESCC in the present study.We detected the expression of Chk2, Cyclin D1 and Cdc25C in pretreatment biopsy specimen and NF-κB in pretreatment and postreatment speicman by immunohistochemistry in patients with ESCC. Then the correlation of Chk2, Cyclin D1 and Cdc25C overexpression with clinical parameters was evaluated. Our results revealed overexpression of Cdc25C was significantly associated with pathCR and better survival in this series of patients. In addition, activation of NF-κB in postreatment specimen was associatied with a poor survival.To further explore the potential effect of Cdc25C and NF-κB in the radiotherapy of ESCC, plasmid of Cdc25C was transfected in KSYE150 cell line transistently. And small molecule inhibitors were used to inhibit the function of Cdc25C and NF-κB. After different dose of radiation, FCM test were used to detect the change of cell cycle. Clony formation test, as a golden standard to prove the radiosensitivity of cells, was used to prove the radiosensitivity of different groups. Western blot and EMSA were used to detect expression and activation of target genes. Our result could not demonstrate the radiosensitivity in cells that transistently transfected Cdc25C plsmid for the lack of transfection efficacy. But BN82002, an inhibitor of Cdc25C, has an effect on the cell cycle and its radiation response significantly. Our data show that BN82002 decrease the radiosensitivity by accelerating cell cycle. Meanwhile, we detected the strongest activation of NF-κB at the dose of 12Gy after radiation of 3 hours. SN50, enhanced radiosensitivity in esophageal cells by inhibit the function of NF-κB. Taken together, our result demonstrate that overexpression of Cdc25C was associated with radiation response and treatment outcome. Inhibition the function of Cdc25C decrease the radiosensitivity by accelerating cell cycle. Activation of NF-κB was associatied with a poor survival in postreatment specimen. Enhanced radiosensitivity of ESCC cells was also oberserved by inhibiting the activation of NF-κB. These data suggest that Cdc25C and NF-κB may play an important role in the signal pathway of radiation response.