Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha

Kotaro Miyake, Kunihiro Tsuchida, Hiromu Sugino, Satoru Imura, Yuji Morine, Masahiko Fujii, Mitsuo Shimada

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: We evaluated the antitumor and antiangiogenic activities of human natural interferon-alpha (IFN-α) alone or in combination with S-1 against human pancreatic cancer cells. Methods: Three days after the subcutaneous (s.c.) implantation of tumor cells, mice (n = 12) were received s.c. injection with IFN-α alone (10,000 U six times a week), oral administration with S-1 alone (8 mg/kg six times a week), or both with IFN-α and S-1 (8, 10, 12 mg/kg six times a week). Results: Administration of IFN-α in combination with S-1 significantly decreased progressive growth and angiogenesis of human pancreatic cancer cells. The combination therapy produced more significant inhibition in expression of the representative proangiogenic molecules, vascular endothelial growth factor and basic fibroblast growth factor than individual treatment either IFN-α or S-1 alone did. These treatments also decreased the staining of proliferating cell nuclear antigen, induced apoptosis and decreased microvessel density. In order to better understand the precise molecular mechanisms by which IFN-α and S-1 exert its effects, we have utilized cDNA microarray including 124 known genes to determine the gene expression profile altered by IFN-α and S-1 treatment. We found a total of seven genes which showed a twofold change after IFN-α and S-1 treatment in addition to VEGF, bFGF, CD31, MMP-2, MMP-7 and MMP-9. Among these genes, we found down-regulation of six genes and up-regulation of one gene, which are related to angiogenesis, tumor cell invasion and metastasis. Conclusions: These data suggest that administration of IFN-α in combination with S-1 may provide a novel and effective approach to the treatment of human pancreatic cancer.

Original languageEnglish
Pages (from-to)113-126
Number of pages14
JournalCancer Chemotherapy and Pharmacology
Volume59
Issue number1
DOIs
Publication statusPublished - 01-01-2007

Fingerprint

Pancreatic Neoplasms
Interferon-alpha
Nude Mice
Antineoplastic Agents
Genes
Matrix Metalloproteinases
Cells
Therapeutics
Vascular Endothelial Growth Factor A
Tumors
Proliferating Cell Nuclear Antigen
Fibroblast Growth Factor 2
Subcutaneous Injections
Microarrays
Microvessels
Oligonucleotide Array Sequence Analysis
Transcriptome
Gene expression
Human Activities
Oral Administration

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Miyake, Kotaro ; Tsuchida, Kunihiro ; Sugino, Hiromu ; Imura, Satoru ; Morine, Yuji ; Fujii, Masahiko ; Shimada, Mitsuo. / Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha. In: Cancer Chemotherapy and Pharmacology. 2007 ; Vol. 59, No. 1. pp. 113-126.
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abstract = "Purpose: We evaluated the antitumor and antiangiogenic activities of human natural interferon-alpha (IFN-α) alone or in combination with S-1 against human pancreatic cancer cells. Methods: Three days after the subcutaneous (s.c.) implantation of tumor cells, mice (n = 12) were received s.c. injection with IFN-α alone (10,000 U six times a week), oral administration with S-1 alone (8 mg/kg six times a week), or both with IFN-α and S-1 (8, 10, 12 mg/kg six times a week). Results: Administration of IFN-α in combination with S-1 significantly decreased progressive growth and angiogenesis of human pancreatic cancer cells. The combination therapy produced more significant inhibition in expression of the representative proangiogenic molecules, vascular endothelial growth factor and basic fibroblast growth factor than individual treatment either IFN-α or S-1 alone did. These treatments also decreased the staining of proliferating cell nuclear antigen, induced apoptosis and decreased microvessel density. In order to better understand the precise molecular mechanisms by which IFN-α and S-1 exert its effects, we have utilized cDNA microarray including 124 known genes to determine the gene expression profile altered by IFN-α and S-1 treatment. We found a total of seven genes which showed a twofold change after IFN-α and S-1 treatment in addition to VEGF, bFGF, CD31, MMP-2, MMP-7 and MMP-9. Among these genes, we found down-regulation of six genes and up-regulation of one gene, which are related to angiogenesis, tumor cell invasion and metastasis. Conclusions: These data suggest that administration of IFN-α in combination with S-1 may provide a novel and effective approach to the treatment of human pancreatic cancer.",
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Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha. / Miyake, Kotaro; Tsuchida, Kunihiro; Sugino, Hiromu; Imura, Satoru; Morine, Yuji; Fujii, Masahiko; Shimada, Mitsuo.

In: Cancer Chemotherapy and Pharmacology, Vol. 59, No. 1, 01.01.2007, p. 113-126.

Research output: Contribution to journalArticle

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T1 - Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha

AU - Miyake, Kotaro

AU - Tsuchida, Kunihiro

AU - Sugino, Hiromu

AU - Imura, Satoru

AU - Morine, Yuji

AU - Fujii, Masahiko

AU - Shimada, Mitsuo

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N2 - Purpose: We evaluated the antitumor and antiangiogenic activities of human natural interferon-alpha (IFN-α) alone or in combination with S-1 against human pancreatic cancer cells. Methods: Three days after the subcutaneous (s.c.) implantation of tumor cells, mice (n = 12) were received s.c. injection with IFN-α alone (10,000 U six times a week), oral administration with S-1 alone (8 mg/kg six times a week), or both with IFN-α and S-1 (8, 10, 12 mg/kg six times a week). Results: Administration of IFN-α in combination with S-1 significantly decreased progressive growth and angiogenesis of human pancreatic cancer cells. The combination therapy produced more significant inhibition in expression of the representative proangiogenic molecules, vascular endothelial growth factor and basic fibroblast growth factor than individual treatment either IFN-α or S-1 alone did. These treatments also decreased the staining of proliferating cell nuclear antigen, induced apoptosis and decreased microvessel density. In order to better understand the precise molecular mechanisms by which IFN-α and S-1 exert its effects, we have utilized cDNA microarray including 124 known genes to determine the gene expression profile altered by IFN-α and S-1 treatment. We found a total of seven genes which showed a twofold change after IFN-α and S-1 treatment in addition to VEGF, bFGF, CD31, MMP-2, MMP-7 and MMP-9. Among these genes, we found down-regulation of six genes and up-regulation of one gene, which are related to angiogenesis, tumor cell invasion and metastasis. Conclusions: These data suggest that administration of IFN-α in combination with S-1 may provide a novel and effective approach to the treatment of human pancreatic cancer.

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