Rh2 or its aglycone aPPD in combination with docetaxel for treatment of prostate cancer.
BACKGROUND
Docetaxel is one of the few chemotherapeutic drugs that are considered highly effective when used to treat prostate cancer patients that have relapsed and/or metastatic disease, it is therefore reasonable to expect further improvements in treatment outcomes when it is combined with other therapeutic agents active in prostate cancer. This study assesses the combination of well tolerated and orally bioavailable formulations of ginsenoside Rh2 or its aglycone aPPD with docetaxel.


METHODS
The in vitro activity of Rh2, aPPD, and docetaxel was determined in four prostate cancer cell lines: PC-3, LNCaP, DU145, and C4-2. Combinations of Rh2 or aPPD with docetaxel were assessed using the constant ratio combination design. Combination Indices (CI) and Dose Reduction Indices (DRI) were subsequently estimated using Calcusyn. In vivo efficacy studies and Immunohistochemical analyses (PC-3 model) were also evaluated.


RESULTS
In PC-3, DU145 and C4-2 prostate cancer cells combinations of Rh2 or aPPD with docetaxel were predominantly additive or synergistic. Combinations of Rh2 + docetaxel and aPPD + docetaxel caused established PC-3 tumors to regress from their initial size by 15% and 27%, respectively. Tumor cell proliferation rate (measured by Ki-67 positive cells) was significantly lower for combinations of Rh2 + docetaxel and aPPD + docetaxel, compared to animals treated with docetaxel alone.


CONCLUSIONS
Rh2 and aPPD can be combined with docetaxel to yield additive or synergistic activity in vitro and in vivo. Pending further assessment of toxicity and pharmacodynamic behavior, this study supports testing of combinations of ginsenoside Rh2 or its aglycone aPPD with docetaxel in a clinical setting.
Musende
Alain G
AG
The Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada.
Eberding
Andy
A
Jia
William
W
Ramsay
Euan
E
Bally
Marcel B
MB
Guns
Emma Tomlinson
ET
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D036145:Ginsenosides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D043823:Taxoids; D000077143:Docetaxel; C055305:ginsenoside Rh2