Synergistic Effect of Geranylgeranyltransferase Inhibitor, GGTI, and Docetaxel on the Growth of Prostate Cancer Cells
Most advanced prostate cancers progress to castration resistant prostate cancer (CRPC) after a few years of androgen deprivation therapy and the prognosis of patients with CRPC is poor. Although docetaxel and cabazitaxel can prolong the survival of patients with CRPC, inevitable progression appears...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2012/989214 |
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| Summary: | Most advanced prostate cancers progress to castration resistant
prostate cancer (CRPC) after a few years of androgen deprivation
therapy and the prognosis of patients with CRPC is poor. Although
docetaxel and cabazitaxel can prolong the survival of patients
with CRPC, inevitable progression appears following those
treatments. It is urgently required to identify better or
alternative therapeutic strategies. The purpose of this study was
to confirm the anti-cancer activity of zoledronic acid (Zol) and
determine whether inhibition of geranylgeranylation in the
mevalonate pathway could be a molecular target of prostate cancer
treatment. We examined the growth inhibitory effect of Zol in
prostate cancer cells (LNCaP, PC3, DU145) and investigated a role
of geranylgeranylation in the anticancer activity of Zol. We,
then, evaluated the growth inhibitory effect of
geranylgeranyltransferase inhibitor (GGTI), and analyzed the
synergy of GGTI and docetaxel by combination index and
isobolographic analysis. Zol inhibited the growth of all prostate
cancer cell lines tested in a dose-dependent manner through
inhibition of geranylgeranylation. GGTI also inhibited the
prostate cancer cell growth and the growth inhibitory effect was
augmented by a combination with docetaxel. Synergism between GGTI
and docetaxel was observed across a broad range of concentrations.
In conclusion, our results demonstrated that GGTI can inhibit the
growth of prostate cancer cells and has synergistic effect with
docetaxel, suggesting its potential role in prostate cancer
treatment. |
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| ISSN: | 2090-3111 2090-312X |