Chemosensitivity of human pancreatic carcinoma cells is enhanced by IkBα super-repressor

Pancreatic cancer has an unfavorable prognosis; surgery and chemotherapy at present have only limited value. To improve the prognosis of pancreatic cancer, effective non-surgical therapy is necessary. NF-kB is reported to be related to resistance to apopto-sis, but its role in Chemosensitivity remains controversial. We examined the effects on Chemosensitivity of inhibition by induction of the super-repressor IkBα in pancreatic cancer cell lines, BxPC-3, Capan-1 and Panc-1. IkBα protein was transduced by infection of adenovirus vector AxCAhlkBδN. Sensitivity to VP-16 and doxorubicin was increased significantly by IkBα induction in all three pancreatic cell lines. To investigate molecular events during IkBα induction, we examined the changes in expression of drug-resistance-related genes by real-time RT-PCR and those in apoptosis-related genes by cDNA microarray. There was no common change of gene expression before and after IkBα induction among the three pancreatic cancer cell lines, except for mdm2. Further examination of other genes is necessary for a better understanding of the molecular mechanisms of enhancement of Chemosensitivity through IkBα induction. However, we have confirmed that IkBα induction leads to an increase of Chemosensitivity of pancreatic cancer. Many problems remain before clinical application of this adenoviral system will be feasible, but our results may ultimately lead to an improved therapy of pancreatic cancer. (Cancer Sci 2003; 94: 467–472)