Abstract 213: Combinative treatment for prostate cancer by adenoviral-mediated gene therapy expressing a novel apoptosis gene and chemotherapy

Abstract

Abstract A novel gene, rat pHyde, and its human homologue, hpHyde, have been cloned from prostate cancer cells. Database search and FISH analysis consistently indicated that hpHyde gene localizes at human chromosome 2q14. Protein sequence analysis suggests that hpHyde may be a plasma membrane protein with calcium channel function. hpHyde is differentially expressed in various normal human tissues and organs, suggesting that hpHyde may play roles in development and differentiation. A recombinant adenovirus containing pHyde cDNA gene (AdRSVpHyde) showed significant growth inhibition on human prostate cancer cells, both in vitro and in vivo, through a caspase-3 dependent apoptosis induction. The anti-prostate cancer effects of pHyde in conjunction with chemotherapy agent were analyzed by in vitro and in vivo assays using AdRSVpHyde in combination with DNA damaging chemotherapeutic agent, cisplatin, and docetaxel, respectively. Growth suppression and induction of apoptosis were additively greater in DU145 human prostate cancer cells treated with AdRSVpHyde and cisplatin than either agent alone both in vitro and in vivo. Moreover, AdRSVpHyde and docetaxel also have a similar additively inhibitory effect on DU145 cell growth. Taken together, these results support the potential use of pHyde for prostate cancer gene therapy coupled with chemotherapy to improve therapeutic index. Our results also suggest that pHyde may play important physiological and pathological roles in normal prostate development and prostate carcinogenesis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 213.