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Antisense down-regulation of 5-FU related enhances cytotoxicity of 5-FU in human lung cancer

Research Project

Project/Area Number 13671237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTHE University of Tokushima

Principal Investigator

KONDO Kazuya  University of Tokushima, school of medicine, Assistant Professor, 医学部, 講師 (10263815)

Co-Investigator(Kenkyū-buntansha) MIYOSHI Takanori  University of Tokushima, university hospital, Assistant, 医学部附属病院, 助手 (20346612)
MONDEN Yasumasa  University of Tokushima, school of medicine, Professor, 医学部, 教授 (60028628)
滝沢 宏光  徳島大学, 医学部・附属病院, 医員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsantisense / oligodeoxynucleotide / thymidylate synthase / liposome / lung cancer / 5-FU / thymidylate synthase / antisense oligonucleotide / HVJ-リポソーム
Research Abstract

Thymidylate synthase (TS), the key enzyme in de novo synthesis of thymidine, is an important target for antitumor chemothrapy of 5-FU. We used antisense oligodeoxynucleotide (ODN) to down-regulate the expression of TS. We made 5 antisense ODNs which is complementary to TS Mrna, and one random ODN. Transfection of ODNs was performed using HVJ-liposome. After incubating human lung cancer cell lines (Ma10 and Ma25) and antisense ODNs with HVJ-liposome, the TS expression of cell lines was examined by RT-PCR method and TS activity was measured. TS expression was repressed from 50% to 20% by incubaating cell lines and antisense ODNs and TS expression. It was impossible that antisense ODNs of TS inhibited the expression of TS. Chu e al. reported that the TS protein itself binds to the T Mrna both at the translational start site and in the coding region, inhibiting translational processing of the message.
Next year, we examined whether CDDP (anticancer drug) conjugated by liposome (liposome-CDDP) enhance anticancer effect. The IC50 of CDDP was 40ug/ML in human lung cancer cell line Ma44-3 in vitro. Meanwhile, the IC50 of liposome-CDDP was 10ug/ML for 48 hr incubation. And it was 1.5ug/ML for 96 hr incubation. When thecubation time becomes longer, the IC50 of liposome-CDDP was lower. The use of Rhodamine-labeled liposome-CDDP revealed that the lipsome-CDDP attached the cytoplasm of cancer cells in vitro. Rhodamine-labeled liposome-CDDP revealed that the liposome-CDDP attached the cytoplasm of cancer cells in vitro. Rhodamine-labeled liposome-CDDP was administrared in SCID mice using a nebulizer (through airway). Rhodamine-labeled liposome was observed in the lung of the mice. These results demonstrate that the administration of liposome-CDDP through airway may become a therapy for lung cancer.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Toshiyuki Hirose: "Frequent Microsatellite Instability in Lung Cancer From Chromate-Exposed Workers"MOLECULAR CARCINOGENESIS. 33. 172-180 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 近藤 和也: "比較的まれな肺癌に対する最近の治療戦略"日本臨床. 60・5. 550-553 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 近藤 和也: "肺の多発癌の治療"胸部外科. 55・1. 4-9 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 近藤 和也: "肺小細胞癌の治療指針"外科治療. 87・3. 313-314 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuya Kondo: "Occupational Cancer Genetics : Infrequent ras Oncogenes Point Mutations in Lung Cancer Sammples From Chromate Workers"American Journal of Industrial medicne. 40. 92-97 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuya Kondo: "Multilocular Thymic Cyst Assosiated Wth Sjogren's Syndrome"Ann.Thorac.Surg. 72. 1367-1369 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiyuki Hirose: "Frequent Microsatellite Instability in Lung Cancer From Chromate-Exposed Workers"MOLECULAR CARCINOGENESIS. 33. 172-180 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuya Kondo: "Occupational Cancer Genetics: Infrequent ras Oncogenes Point Mutations in Lung Cancer Sammples From Chromate Workers"American Journal of Industrial medicne. 40. 92-97 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuya Kondo: "Multilocular Thymic Cyst Assosiated Wth Sjogren's Syndrome"Ann. Thorac. Surg. 72. 1367-1369 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiyuki Hirose: "Frequent Microsatellite Instability in Lung Cancer From Chromate-Exposed Workers"MOLECULAR CARCINOGENESIS. 33. 172-180 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 近藤 和也: "比較的まれな肺癌に対する最近の治療戦略"日本臨床. 60・5. 550-553 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 近藤 和也: "肺の多発癌の治療"胸部外科. 55・1. 4-9 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 近藤 和也: "肺小細胞癌の治療指針"外科治療. 87・3. 313-314 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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