Tumor growth suppression by adenovirus-mediated introduction of a cell-growth-suppressing gene tob in a pancreatic cancer model.
TOB (transducer of ErbB-2) is a tumor suppressor that interacts with protein-tyrosine kinase receptors, including ErbB-2. Introduction of the tob gene into NIH3T3 cells results in cell growth suppression. In this study, we evaluated the effect of tob expression in pancreatic cell lines (AsPC-1, BxPC-3, SOJ) and discuss the tumor-suppressing effects of adenoviral vector expressing tob cDNA. We first measured the levels of endogenous tob mRNA being expressed in all pancreatic cancer cell lines. Then, we examined the effect of adenoviral vector containing tob cDNA (Ad-tob vector) on cancer cell lines. The viral vector was expanded with transfection in 293 cells. The titer of the vector was 350x10(6) pfu/ml. These cancer cells were able to be transfected with MOI 20 without adenoviral toxicity. The transfection of Ad-tob vector results in growth suppression of SOJ and AsPC-1 cell lines. The magnitude of the expression of the Ad-tob gene in cancer is correlated to tumor suppressive activity. We prepared pancreatic cancer peritonitis models using a peritoneal injection of AsPC-1 cells. In this model, bloody ascites and multiple tumor nodules were seen at the mesentery after 16 days. AdCAtob (50x10(6) pfu/day) was administered from day 5 to day 9 after 4 days of peritoneal injection of 2x10(6) AsPC-1 cells. Tumor growth suppression occurred 10 days after peritoneal injection of AdCAtob compared with the control group. There were no tumor nodules in the abdomen and no bloody ascites. These results suggest that the peritoneal injection of AdCAtob has potential to suppress the formation of pancreatic cancer peritonitis, and can be applied for chemotherapy-resistant cancer peritonitis.
Yanagie
Hironobu
H
Department of Cardiac Surgery, University of Tokyo Hospital, Tokyo, Japan. yanagie@n.t.u-tokyo.ac.jp
Tanabe
Tuyoshi
T
Sumimoto
Hidetoshi
H
Sugiyama
Hirotaka
H
Matsuda
Satoru
S
Nonaka
Yasumasa
Y
Ogiwara
Naoko
N
Sasaki
Katsunori
K
Tani
Kensaburo
K
Takamoto
Shinichi
S
Takahashi
Hiroyuki
H
Eriguchi
Masazumi
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002277:Carcinoma / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D002455:Cell Division; D045744:Cell Line, Tumor / Q000637:transplantation; D003360:Cosmids / Q000235:genetics; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins