A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors

Chia Ling Hsieh, Haiyen E. Zhau, Leland W.K. Chung, Chia Ling Hsieh, Ling Yang, Li Miao, Fang Yeung, Haiyen E. Zhau, Leland W.K. Chung, Chinghai Kao, Hua Yang

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We report the development of a novel replication-competent adenoviral vector, Ad-hOC-E1, containing a single bidirectional human osteocalcin (hOC) promoter to drive both the early viral E1A and E1B gene. This vector selectively replicated in OC-expressing but not non-OC-expressing cells, with viral replication enhanced at least 10-fold on vitamin D3 exposure. Both the artificial TATA-box and hOC promoter element in this bidirectional promoter construct were controlled by a common OC regulatory element which selectively activated OC expression in cells. The expression of E1A and E1B gene by Ad-hOC-E1 can be markedly induced by vitamin D3. Unlike Ad-sPSA-E1, an adenoviral vector with viral replication controlled by a strong super prostate-specific antigen (sPSA) promoter which only replicates in PSA-expressing cells with androgen receptor (AR), Ad-hOC-E1 retarded the growth of both androgen-dependent and androgen-independent prostate cancer cells irrespective of their basal level of AR and PSA expression. A single i.v. administration of 2 × 109 plaque-forming units of Ad-hOC-E1 inhibited the growth of previously established s.c. DU145 tumors (an AR- and PSA-negative cell line). Viral replication is highly enhanced by i.p. administration of vitamin D3. Ultimately, enhancing Ad-hOC-E1 viral replication by vitamin D3 may be used clinically to treat localized and osseous metastatic prostate cancer in men.

Original languageEnglish (US)
Pages (from-to)3084-3092
Number of pages9
JournalCancer Research
Volume62
Issue number11
StatePublished - Jun 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hsieh, C. L., Zhau, H. E., Chung, L. W. K., Hsieh, C. L., Yang, L., Miao, L., Yeung, F., Zhau, H. E., Chung, L. W. K., Kao, C., & Yang, H. (2002). A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors. Cancer Research, 62(11), 3084-3092.