Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice.
BACKGROUND
Ginsenoside Rg3, a saponin extracted from ginseng, inhibits angiogenesis. The combination of low-dose chemotherapy and anti-angiogenic inhibitors suppresses growth of experimental tumors more effectively than conventional therapy or anti-angiogenic agent alone. The present study was designed to evaluate the efficacy of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis and growth of established Lewis lung carcinoma in mice.


METHODS
C57L/6 mice implanted with Lewis lung carcinoma were randomized into the control, ginsenoside Rg3, gemcitabine and combination group. The quality of life and survival of mice were recorded. Tumor volume, inhibitive rate and necrosis rate were estimated. Necrosis of tumor and signals of blood flow as well as dynamic parameters of arterial blood flow in tumors such as peak systolic velocity (PSV) and resistive index (RI) were detected by color Doppler ultrasound. In addition, expression of vascular endothelial cell growth factor (VEGF) and CD31 were observed by immunohistochemstry, and microvessel density (MVD) of the tumor tissues was assessed by CD31 immunohistochemical analysis.


RESULTS
Quality of life of mice in the ginsenoside Rg3 and combination group were better than in the control and gemcitabine group. Combined therapy with ginsenoside Rg3 and gemcitabine not only enhanced efficacy on suppression of tumor growth and prolongation of the survival, but also increased necrosis rate of tumor significantly. In addition, the combination treatment could obviously decrease VEGF expression and MVD as well as signals of blood flow and PSV in tumors.


CONCLUSIONS
Ginsenoside Rg3 combined with gemcitabine may significantly inhibit angiogenesis and growth of lung cancer and improve survival and quality of life of tumor-bearing mice. The combination of chemotherapy and anti-angiogenic drugs may be an innovative and promising therapeutic strategy in the experimental treatment of human lung cancer.
Liu
Tai-Guo
TG
Division of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China. liutaiguo031@126.com
Huang
Ying
Y
Cui
Dan-Dan
DD
Huang
Xiao-Bing
XB
Mao
Shu-Hua
SH
Ji
Ling-Ling
LL
Song
Hai-Bo
HB
Yi
Cheng
C
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000093542:Gemcitabine
D036145:Ginsenosides; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; C097367:ginsenoside Rg3; D000093542:Gemcitabine