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Updated: Jul 4, 2026
Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
Effects of Eg5 knockdown on human prostate cancer xenograft growth and chemosensitivity
Norihiro Hayashi1, Erich Koller, Ladan Fazli
1The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
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.
Insights
Eg5 gene targeting with antisense oligonucleotides (ASO) shows promise for inhibiting prostate cancer (CaP) growth. However, combining Eg5 ASO with paclitaxel did not improve outcomes and may be detrimental.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Microtubular inhibitors like docetaxel are effective in prostate cancer (CaP).
- The Eg5 gene (kinesin-5 family) is crucial for mitotic spindle function and a potential target in proliferating cancer cells.
- Androgen-independent CaP presents a therapeutic challenge.
Purpose of the Study:
- To investigate the functional activity and anti-cancer potential of Eg5 antisense oligonucleotide (ASO) in androgen-independent CaP.
- To assess the efficacy of Eg5 ASO treatment both in vitro and in vivo.
- To evaluate combination therapy with paclitaxel.
Main Methods:
- Utilized an antisense oligonucleotide (ASO) targeting the Eg5 gene.
- Assessed Eg5 mRNA and protein levels in PC3 and LNCaP CaP cell lines.
- Evaluated cell growth, cell cycle arrest (G2/M phase), and apoptosis in vitro.
- Conducted in vivo studies using xenograft models of CaP.
Main Results:
- Eg5 ASO treatment reduced Eg5 mRNA and protein levels in a dose-dependent manner.
- Eg5 ASO inhibited CaP cell growth, induced G2/M phase arrest, and increased apoptosis.
- Low-dose Eg5 ASO antagonized paclitaxel's cytotoxic effects.
- In vivo, Eg5 ASO monotherapy reduced tumor growth, but combination with paclitaxel showed no additive benefit.
Conclusions:
- Eg5 is a viable molecular target for delaying androgen-independent CaP progression.
- Combination therapy of Eg5 ASO with paclitaxel is not recommended due to potential antagonism.
- Further research into Eg5-targeted therapies for CaP is warranted.
