Enhancement of antitumor effects of paclitaxel (taxol) in combination with red ginseng acidic polysaccharide (RGAP).
We have recently reported that red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), shows immunomodulatory and antitumor activities, mainly mediated by the nitric oxide (NO) production of macrophages. This compound may be used in cancer therapy alone or in combination with other chemotherapeutic agents. The synergistic effect of RGAP and paclitaxel (taxol) was evaluated to develop new biological response modifiers in cancer therapy. The present study demonstrates a synergistic antitumor effect of RGAP and paclitaxel in mice transplanted with sarcoma 180 and B16 melanoma. Combined treatment with paclitaxel (5 or 15 mg/kg) and RGAP (25 mg/kg) resulted in a 28.6 or 42.8 % increase in the life span of ICR mice bearing sarcoma 180 tumor cells, while no obvious effect was seen on sole paclitaxel treatment. When a combination of paclitaxel (10 mg/kg) and RGAP (100 mg/kg) was administered to C57BL/6 mice implanted with B16 melanoma, the tumor weight per mouse also decreased by 76.3 %, suggesting that RGAP may be used as an adjuvant in medicinal applications of paclitaxel. The augmented antitumor effect of paclitaxel is supposed to be the result of the immunomodulating antitumor effect of RGAP. RGAP, having B cell specific mitogenic activity, induced the secretion of interleukin-6 (IL-6) in spleen cells in a concentration-dependent manner (5 to 500 microg/microL). RGAP also restored the proliferation of splenocytes and NK cell activity suppressed by paclitaxel. Flow cytometric analysis of splenocytes in mice treated with paclitaxel showed a significant increase of CD11b+ cells. Additionally, a synergistic effect of RGAP and paclitaxel was found to effect an increased tumoricidal activity of macrophages. The above results suggest that clinical trials of RGAP as an adjuvant in cancer chemotherapy of paclitaxel are highly feasible.
Shin
Han Jae
HJ
KT&G Central Research Institute, Daejeon, Korea.
Kim
Young Sook
YS
Kwak
Yi Seong
YS
Song
Yong Bum
YB
Kim
Young Sang
YS
Park
Jong Dae
JD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000008:administration & dosage*; D005894:Panax; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D011134:Polysaccharides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; D015850:Interleukin-6; D010936:Plant Extracts; D011134:Polysaccharides; D017239:Paclitaxel