1996 Fiscal Year Final Research Report Summary
Gene Therapy for Colon Cancer with Adenoviral Vector Expressing Tumor Suppressor p53 Gene
| Project/Area Number |
07671393
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Okayama University |
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Principal Investigator |
HIZUTA Akio Okayama Univ.Med.Sch., First Dept.Surg., Assistant Prof., 医学部・附属病院, 講師 (60199007)
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| Co-Investigator(Kenkyū-buntansha) |
YASUDA Tatsuji Okayama Univ.Med.Sch., Dept.Cell Chem., 医学部, 教授 (30092357)
FUJIWARA Toshiyoshi Okayama Univ.Med.Sch., First Dept.Surg., 医学部・附属病院, 医員
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| Project Period (FY) |
1995 – 1996
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| Keywords | p53 / Gene Therapy / Colon Cancer / Cisplatin |
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| Research Abstract |
The alteration of wild-type p53 gene by mutations, deletions, or rearrangements is a major factor in the development of human colon cancer. Recent studies have demonstrated that p53 might be an essential component of the cytotoxic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined the antitumor effect of adenovirus-mediated wild-type p53 gene transfer in combination with a chemotherapeutic drug on human colon cancer cell line WiDr, which has a homozygous mutated p53 gene. The treatment with a chemotherapeutic drug, cisplatin, following the infection of a replication-deficient, recombinant adenoviral vector expressing wt-p53 (termed AdCMV p53) significantly suppressed the growth of WiDr cells compared to any single treatments. To evaluate the in vivo efficacy of AdCMV p53 and cisplatin given in a sequential combination, WiDr cells were subcutaneously inoculated in nu/nu mice, and after 3 days AdCMV p53 was subcutaneously injected into the area where tumor cells were implanted followed by intraperitoneal administration of cisplatin. Analysis of initial growth inhibition at 21 days demonstrated a profound, therapeutic cooperativity, although AdCMV p53 alone or cisplatin alone showed a modest slowing of the tumor growth. These results suggest that the gene therapy using wt-p53-expressing a denovirus in combination with a chemotherapeutic DNA-damaging drug is a useful strategy for human colon cancer therapy.
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