The cancer-associated Sm-like oncogene: a novel target for the gene therapy of pancreatic cancer.
BACKGROUND
The prognosis for pancreatic cancer (PC) remains dismal, providing a clear need for the development of novel therapies. We have previously shown that the cancer-associated Sm-like (CaSm) oncogene is overexpressed in the great majority of pancreatic tumors and is required to maintain the transformed phenotype. The purpose of this study was to determine whether the application of CaSm antisense gene therapy would generate a significant antitumor effect against PC.


METHODS
An adenoviral vector (Ad-alphaCaSm) expressing a 900-base pair antisense RNA to CaSm was created. The PC cell lines AsPC-1 and Capan-1 were infected with this vector and examined for changes in in vitro proliferation by using methyl thiazol tetrazolium and soft agar assays. SCID-Bg mice bearing subcutaneous AsPC-1 tumors were treated with Ad-alphaCaSm (1 x 10(9) plaque-forming units) as a single intratumor injection with tumor growth and survival monitored.


RESULTS
AsPC-1 and Capan-1 cells showed decreased in vitro proliferation (93%, P =.0041, and 70%, P =. 0038, respectively) and anchorage independent growth (55%, P =.02, and 45%, P =.03, respectively) after treatment. Ad-alphaCaSm reduced in vivo AsPC-1 tumor growth by 40% (n = 10), extending median survival time from 35 to 60 days.


CONCLUSIONS
Ad-alphaCaSm demonstrates a significant antitumor effect against pancreatic cancer both in vitro and in vivo. These results support the role of CaSm as a significant gene involved in the neoplastic transformation of pancreatic tumors. Thus CaSm represents a novel gene target in PC and holds potential as a new treatment approach either alone or in combination with existing therapies.
Kelley
J R
JR
Department of Surgery, Center for Molecular and Structural Biology, and Hollings Cancer Center, Medical University of South Carolina, Charleston 29425, USA.
Brown
J M
JM
Frasier
M M
MM
Baron
P L
PL
Schweinfest
C W
CW
Vournakis
J N
JN
Watson
D K
DK
Cole
D J
DJ
D000256:Adenoviridae; D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D051379:Mice; D016513:Mice, SCID; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D016372:RNA, Antisense; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016372:RNA, Antisense