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Prostate. 2008 Sep 1;68(12):1283-95. doi: 10.1002/pros.20783.

Effects of Eg5 knockdown on human prostate cancer xenograft growth and chemosensitivity.

Author information

1
The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Abstract

OBJECTIVES:

Microtubular inhibitors, including docetaxel, are active cytotoxics in many cancers, including prostate cancer (CaP). The Eg5 gene, a member of the kinesin-5 family, plays critical roles in proper mitotic spindle function, and is a potential microtubule-related target for proliferating cancer cells. To investigate the functional activities of Eg5 in CaP, we used an antisense oligonucleotide (ASO) targeting Eg5 to assess the potency and anti-cancer activity of Eg5 ASO treatment for androgen-independent CaP cells in vitro and in vivo.

RESULTS:

PC3 cells express higher Eg5 protein and mRNA levels compared to LNCaP cells. In both cell lines, Eg5 ASO treatment reduced mRNA and protein levels in a dose-dependent manner and a complete reduction of Eg5 protein levels was observed at 100 nM. Dose-dependent inhibition in cell growth, potent G2/M phase arrest, and increases in apoptotic sub-G1 fraction were also observed using Eg5 ASO. Surprisingly, low dose Eg5 ASO significantly antagonized cytotoxic effects of paclitaxel. In vivo, Eg5 ASO monotherapy significantly reduced both LNCaP and PC-3 tumor growth but combination treatment with paclitaxel did not yield additive benefits.

CONCLUSIONS:

These findings suggest that while Eg5 is a potential target to delay androgen-independent CaP growth, combination treatment with paclitaxel may not be desirable.

PMID:
18512732
DOI:
10.1002/pros.20783
[Indexed for MEDLINE]

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