Evaluation Of Antitumor Activity Of SC263in22RV1Prostate Tumor Xenograft Model Of Nude Mice In Vivo

Prostate cancer is the second most prevalent cause of death in men in the USA and Europe. Incidence rates which are generally low in Asian countries have risen proportionately more than in western world in recent years. The androgen receptor (AR), a receptor of nuclear family and a transcriptional factor, is the most important target for this fatal disease. While most currently available therapies in clinic are directed at reducing the levels of AR-activating androgens, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributed to castration resistant prostate cancer (CRPC) driven by greatly elevated expression of androgen receptors. Once reaching the CRPC stage, prostate cancer will resume growth even in the absence of androgen. A novel therapy under development for treating CRPC is to use a small molecule antiandrogen that competes with androgen for AR-binding to block its transcriptional activity.SC263, a small molecule, which targets the androgen receptor and was designed and synthesized in a cooperator’s lab in Canada. In vitro evaluation showed that SC263binds to AR, blocks its activation and suppresses the proliferation of prostate cancer cell lines. Therefore, whether SC263is effective for suppressing cancer progression in vivo becomes critical for the further development of the small molecule as a clinic therapy. In this study, we establish murine xenografts with the primary22RV1prostate cancer cell line as a proper model to determine the in vivo therapeutic effect of SC263. The results showed that in vivo SC263was also able to bind AR in vivo, inhibited the transcription of its regulated genes as to reduce cancer cell proliferation, and induce apoptosis, which ultimately lowers tumor volume and weight of the SC263treatment group in comparison to the control group. Importantly, no significant toxicity was observed in mice receiving SC263, implying that SC263has significant therapeutic potential for castration resistant prostate cancer.