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Efficient eradication of hormone‐resistant human prostate cancers by inactivated Sendai virus particle
Author(s) -
Kawaguchi Yoshifumi,
Miyamoto Yasuhide,
Inoue Takehiro,
Kaneda Yasufumi
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24234
Subject(s) - du145 , sendai virus , cancer research , prostate cancer , interferon , oncolytic virus , biology , vesicular stomatitis virus , medicine , cancer , virology , virus , endocrinology , lncap
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.