| 抄録 |
Background and Aim：Runt-related transcription factor 3（RUNX3）is a tumor suppressor gene discovered in gastric cancer. RUNX3 is lost or decreased in various cancer tissues, including pancreatic cancer. However, the function of RUNX3 in pancreatic cancer has not been elucidated yet. In the current study, we examined the significance of the decrement of RUNX3 in the pancreatic cancer.
Material and Method：Thirty-six patients with pancreatic cancer who had undergone pancreaticoduodenectomy were enrolled into this study. All patients were administered the 1000mg/m2 gemcitabine after the resection. The expression of RUNX3 and multidrug resistance protein（MRP）expression were examined by immunohistochemistry. The relationship between the prognosis and the expression of RUNX3 was assessed. The pancreatic cancer cell lines MIAPaCa2, PANC1, BxPC3, SUIT2, and KLM1 were used for in vitro study. Ectopic expression of RUNX3 was coordinated by the transfection of RUNX3 cDNA. siRNA against RUNX3 was used to knock down the endogenous RUNX3 expression. We assessed the cell growth and resistance to gemcitabine by MTT assay. The expression of RUNX3 and MRP was assessed by immunoblot analysis.
Result：Median survival of patients was 1006 and 643 days in RUNX3-positive and RUNX3-negative pancreatic cancer, respectively（p=0.014）. Ectopic RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5, while RUNX3 knockdown increased the expression of MRP1, MRP2 and MRP5. Exogenous RUNX3 expression decreases gemcitabine IC50 in RUNX3 negative cells.
Conclusion：Loss of RUNX3 expression induces gemcitabine resistance by increasing MRP expression, resulting in a poor prognosis. |
