Efficient eradication of hormone-resistant human prostate cancers by inactivated Sendai virus particle

Authors

  • Yoshifumi Kawaguchi,

    1. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
    2. Division of Radiation Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Yasuhide Miyamoto,

    1. Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
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  • Takehiro Inoue,

    1. Division of Radiation Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Yasufumi Kaneda

    Corresponding author
    1. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
    • Division of Gene Therapy Science, Osaka University, Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
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Abstract

Hormone-refractory prostate cancer is one of the intractable human cancers in the world. Here, we examined the direct tumor-killing activity of inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] through induction of Type I interferon (IFN) in the hormone-resistant human prostate cancer cell lines PC3 and DU145. Preferential binding of HVJ-E to PC3 and DU145 over hormone-sensitive prostate cancer cell and normal prostate epithelium was observed, resulting in a number of fused cells. After HVJ-E treatment, a number of IFN-related genes were up-regulated, resulting in Type I IFN production in PC3 cells. Then, retinoic acid-inducible gene-I (RIG-I) helicase which activates Type I IFN expression after Sendai virus infection was up-regulated in cancer cells after HVJ-E treatment. Produced IFN-α and -β enhanced caspase 8 expression via Janus kinases/Signal Transducers and Activators of Transcription pathway, activated caspase 3 and induced apoptosis in cancer cells. When HVJ-E was directly injected into a mass of PC3 tumor cells in SCID (severe combined immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was observed and 85% of the mice became tumor-free. Although co-injection of an anti-asialo GM1 antibody with HVJ-E into each tumor mass slightly attenuated the tumor suppressive activity of HVJ-E, significant suppression of tumor growth was observed even in the presence of anti-asialo GM1 antibody. This suggests that natural killer cell activation made small contribution to tumor regression following HVJ-E treatment in hormone-resistant prostate cancer model in vivo. Thus, HVJ-E effectively targets hormone-resistant prostate cancer by inducing apoptosis in tumor cells, as well as activating anti-tumor immunity. © 2009 Wiley-Liss, Inc.

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