Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models.
OBJECTIVE
We explored the efficacy of the ginsenoside Rh2 and examined its impact on the effective dose of paclitaxel and mitoxantrone in the LNCaP prostate tumor model.


METHODS
Cultured LNCaP cell viability was assessed following treatment (48 hours) with Rh2 (0 to 40 microM) alone or in combination with paclitaxel and mitoxantrone. Synergism or antagonism observed when combining treatment was calculated using CalcuSyn software (Biosoft). In addition, the inhibition of LNCaP human xenograft tumor growth was examined in vivo when Rh2 treatment was combined with chemotherapy. Harvested tumors were immunohistochemical stained with p27kip and Ki67.


RESULTS
Rh2 and paclitaxel act synergistically in cultured LNCaP cells to lower ED50 and ED75 values. Rh2 and mitoxantrone are also synergistic. However, when combined as ED95, an antagonistic effect was observed in this cell line. Treatment of LNCaP tumors by Rh2 plus paclitaxel produced a significant decrease in tumor growth and serum prostate specific antigen. Immunohistochemical analysis revealed an apparent but nonsignificant effect on proliferation markers in LNCaP tumors. When Rh2 and mitoxantrone were combined in vivo, there was no significant benefit observed.


CONCLUSIONS
These results indicate that the combination of Rh2 and paclitaxel has an effect on growth inhibition that is greater and synergistic, as demonstrated in a cultured LNCaP cell line. Conversely combining Rh2 with mitoxantrone appears to elicit no benefit. Therefore, combination therapy using chemotherapy and Rh2 requires further investigation.
Xie
Xiaowei
X
Prostate Centre at Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Eberding
Andy
A
Madera
Candice
C
Fazli
Ladan
L
Jia
William
W
Goldenberg
Larry
L
Gleave
Martin
M
Guns
Emma S
ES
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D036145:Ginsenosides / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008942:Mitoxantrone / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; C055305:ginsenoside Rh2; D008942:Mitoxantrone; D017239:Paclitaxel