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Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice.

Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL, Song HB, Yi C - BMC Cancer (2009)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China. liutaiguo031@126.com

ABSTRACT

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.

Conclusion: 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.

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Immunohistochemical staining of CD31 and microvessel density (MVD). A: CD31 (200×). The blood vessels in tumor tissues were stained in yellow brown. a: control group; b: gemcitabine group; c: ginsenoside Rg3 group; d: combination group. B: MVD. MVD was determined by counting the number of microvessels per high-power field (hpf) in the section with an antibody reactive to CD31. ▫P < 0.05 vs control group; □P < 0.05 vs gemcitabine group; ■P < 0.05 vs ginsenoside Rg3 group.
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Figure 5: Immunohistochemical staining of CD31 and microvessel density (MVD). A: CD31 (200×). The blood vessels in tumor tissues were stained in yellow brown. a: control group; b: gemcitabine group; c: ginsenoside Rg3 group; d: combination group. B: MVD. MVD was determined by counting the number of microvessels per high-power field (hpf) in the section with an antibody reactive to CD31. ▫P < 0.05 vs control group; □P < 0.05 vs gemcitabine group; ■P < 0.05 vs ginsenoside Rg3 group.

Mentions: MVD was determined by counting the number of the microvessels per high-power field (hpf) in the section with an antibody reactive to CD31 (Figure 5A). Compared with the control group, MVD value in the ginsenoside Rg3, gemcitabine and combination group decreased obviously, especially in the combination group (P < 0.05) (Figure 5B). There was positive expression of VEGF in the cytoplasm of some tumor cells. The VEGF expression in the ginsenoside Rg3, gemcitabine and combination group was lower than that in the control group (P < 0.05), and VEGF expression in the combination group was lower than in the gemcitabine and ginsenoside Rg3 group (P < 0.05) (Figure 6). The results indicated that ginsenoside Rg3 inhibited tumor angiogenesis and its anti-angiogenic effect was further improved when combined with gemcitabine.


Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice.

Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL, Song HB, Yi C - BMC Cancer (2009)

Immunohistochemical staining of CD31 and microvessel density (MVD). A: CD31 (200×). The blood vessels in tumor tissues were stained in yellow brown. a: control group; b: gemcitabine group; c: ginsenoside Rg3 group; d: combination group. B: MVD. MVD was determined by counting the number of microvessels per high-power field (hpf) in the section with an antibody reactive to CD31. ▫P < 0.05 vs control group; □P < 0.05 vs gemcitabine group; ■P < 0.05 vs ginsenoside Rg3 group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2721848&req=5

Figure 5: Immunohistochemical staining of CD31 and microvessel density (MVD). A: CD31 (200×). The blood vessels in tumor tissues were stained in yellow brown. a: control group; b: gemcitabine group; c: ginsenoside Rg3 group; d: combination group. B: MVD. MVD was determined by counting the number of microvessels per high-power field (hpf) in the section with an antibody reactive to CD31. ▫P < 0.05 vs control group; □P < 0.05 vs gemcitabine group; ■P < 0.05 vs ginsenoside Rg3 group.
Mentions: MVD was determined by counting the number of the microvessels per high-power field (hpf) in the section with an antibody reactive to CD31 (Figure 5A). Compared with the control group, MVD value in the ginsenoside Rg3, gemcitabine and combination group decreased obviously, especially in the combination group (P < 0.05) (Figure 5B). There was positive expression of VEGF in the cytoplasm of some tumor cells. The VEGF expression in the ginsenoside Rg3, gemcitabine and combination group was lower than that in the control group (P < 0.05), and VEGF expression in the combination group was lower than in the gemcitabine and ginsenoside Rg3 group (P < 0.05) (Figure 6). The results indicated that ginsenoside Rg3 inhibited tumor angiogenesis and its anti-angiogenic effect was further improved when combined with gemcitabine.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China. liutaiguo031@126.com

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus