Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts

Satoshi Anai, Steven Goodison, Kathleen Shiverick, Kenneth Iczkowski, Motoyoshi Tanaka, Charles J. Rosser

Research output: Contribution to journalArticle

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Abstract

The resistance of prostate cancers to radiation therapy has been linked to abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition of apoptosis. In this study, we evaluated whether the combination of the overexpression of phosphatase and tensin homolog (PTEN), a protein known to inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of athymic mice. Compared with either treatment alone, the combination of adenoviral vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited xenograft tumor growth. Median tumor size on day 48 was 1030 mm 3 in untreated controls, 656 mm3 in mice treated with radiation (5 Gy) alone, 640 mm3 in mice treated with AdPTEN alone, and 253 mm3 in mice treated with the combination (p < 0.001). Treatment was well tolerated in all cases. Combination treatment also enhanced apoptosis (p = 0.048), inhibited cellular proliferation (p = 0.005), and inhibited tumor-induced neovascularity (p = 0.030). Interestingly, this treatment increased apoptosis not only in tumor cells but also in tumor-associated endothelial cells. Together, these findings indicate that AdPTEN strongly inhibits the growth of human prostate tumors, especially when combined with radiation therapy, and that this effect is mediated by the induction of apoptosis and by the inhibition of angiogenesis and cellular proliferation.

Original languageEnglish (US)
Pages (from-to)975-984
Number of pages10
JournalHuman Gene Therapy
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

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Phosphoric Monoester Hydrolases
Heterografts
Genetic Therapy
Prostatic Neoplasms
Radiation
Growth
Apoptosis
Radiation Dosage
Neoplasms
Radiotherapy
Cell Proliferation
Radiation Effects
Therapeutics
Oncogenes
Nude Mice
Tensins
Prostate
Endothelial Cells
Proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. / Anai, Satoshi; Goodison, Steven; Shiverick, Kathleen; Iczkowski, Kenneth; Tanaka, Motoyoshi; Rosser, Charles J.

In: Human Gene Therapy, Vol. 17, No. 10, 01.10.2006, p. 975-984.

Research output: Contribution to journalArticle

Anai, Satoshi ; Goodison, Steven ; Shiverick, Kathleen ; Iczkowski, Kenneth ; Tanaka, Motoyoshi ; Rosser, Charles J. / Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. In: Human Gene Therapy. 2006 ; Vol. 17, No. 10. pp. 975-984.
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