Monogene and polygene therapy for the treatment of experimental prostate cancers by use of apoptotic genes bax and bad driven by the prostate-specific promoter ARR2PB

Ye Zhang, Jiang Yu, Emmanual Unni, Tsang C. Shao, Bicheng Nan, Thiti Snabboon, Susan Kasper, Francesca Andriani, Larry Denner, Marco Marcelli

Research output: Contribution to journalArticle

19 Scopus citations


We have shown that adenovirus-mediated manipulation of apoptotic genes such as bax could be a therapeutic option for prostate cancer. Unfortunately, the response of experimental prostate tumors to a single therapeutic gene of the apoptotic pathway is short-lived, and most of these tumors relapse after a short period of time. In this investigation we present data generated with adenovirus AvARR2PB-Bad, in which the apoptotic gene bad was placed under the control of the dihydrotestosterone (DHT)-inducible third-generation probasin-derived promoter ARR2PB. This therapeutic virus was given alone or in combination with other therapeutic viruses to a variety of in vitro and in vivo experimental models of prostate cancer. On infection with AvARR2PB-Bad, DHT-induced Bad overexpression occurred specifically in androgen receptor-positive (AR+) cells of prostatic derivation. The apoptotic effect of AvARR2PB-Bad (group 1) was compared with that of AvARR2PB-Bax (which overexpresses the apoptotic protein Bax) (group 2), with that of the combination AvARR2PB-Bad plus AvARR2PB-Bax (group 3), and with that of the control virus AvARR2PB-CAT (group 4) in the cell line LNCaP. In addition to identifying the modality of apoptosis induction by overexpressed Bad, the results suggested that group 3 contained more apoptotic cells than any other group. In additional studies, AR+ androgen-dependent LNCaP cells or AR+ and androgen-independent C4-2 cells were injected subcutaneously into nude mice. Four groups of six LNCaP or C4-2 tumors were treated with the same combinations of viruses discussed above for groups 1, 2, 3, and 4. Treatment resulted in decreased tumor size in groups 1, 2, and 3 compared with group 4. There was a better response in group 3 compared with group 2, and in group 2 compared with group 1. A better response in group 3 was confirmed during a 8-week follow-up period, in which no treatment was administered. Two LNCaP and C4-2 tumors of group 3 disappeared at the end of treatment and did not recur after an 8-week follow-up period. The data suggest that polygene therapy with apoptotic molecules is more effective in experimental models of androgen-dependent or -independent prostate cancer than monogene therapy.

Original languageEnglish (US)
Pages (from-to)2051-2064
Number of pages14
JournalHuman Gene Therapy
Issue number17
StatePublished - Jan 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Monogene and polygene therapy for the treatment of experimental prostate cancers by use of apoptotic genes bax and bad driven by the prostate-specific promoter ARR<sub>2</sub>PB'. Together they form a unique fingerprint.

  • Cite this