Chemosensitivity of human pancreatic carcinoma cells is enhanced by IkappaBalpha 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-kappaB is reported to be related to resistance to apoptosis, but its role in chemosensitivity remains controversial. We examined the effects on chemosensitivity of inhibition by induction of the super-repressor IkappaBalpha in pancreatic cancer cell lines, BxPC-3, Capan-1 and Panc-1. IkappaBalpha protein was transduced by infection of adenovirus vector AxCAhIkBDeltaN. Sensitivity to VP-16 and doxorubicin was increased significantly by IkappaBalpha induction in all three pancreatic cell lines. To investigate molecular events during IkappaBalpha 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 IkappaBalpha 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 IkappaBalpha induction. However, we have confirmed that IkappaBalpha 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.
Sato
Toshiyuki
T
Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Aomori 036-8216, Japan. hodagiri@cc.hirosaki-u.ac.jp
Odagiri
Hiroki
H
Ikenaga
Shojiro-Kazunori
SK
Maruyama
Masateru
M
Sasaki
Mutsuo
M
D000256:Adenoviridae / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis*; D000072000:NF-KappaB Inhibitor alpha; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014162:Transfection
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D009363:Neoplasm Proteins; D000072000:NF-KappaB Inhibitor alpha; D005047:Etoposide; D004317:Doxorubicin