Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model

Wang,Meng; Yan,Shi‑Ju; Zhang,Hong‑Tao; Li,Nan; Liu,Tao; Zhang,Ying‑Long; Li,Xiao‑Xiang; Ma,Qiong; Qiu,Xiu‑Chun; Fan,Qing‑Yu; Ma,Bao‑An

doi:10.3892/ol.2016.5490

Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model

Authors:
- Meng Wang
- Shi‑Ju Yan
- Hong‑Tao Zhang
- Nan Li
- Tao Liu
- Ying‑Long Zhang
- Xiao‑Xiang Li
- Qiong Ma
- Xiu‑Chun Qiu
- Qing‑Yu Fan
- Bao‑An Ma
View Affiliations

Affiliations: Department of Orthopedic Surgery Center and Orthopedic Oncology Institute of People's Liberation Army, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: December 12, 2016 https://doi.org/10.3892/ol.2016.5490
Pages: 681-685
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post‑surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T‑lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma.

View Figures

View References

1	Chu KF and Dupuy DE: Thermal ablation of tumours: Biological mechanisms and advances in therapy. Nat Rev Cancer. 14:199–208. 2014. View Article : Google Scholar : PubMed/NCBI
2	Robinson RD and Knudtson JF: Fertility preservation in patients receiving chemotherapy or radiotherapy. Mo Med. 111:434–438. 2014.
3	Killion JJ and Fidler IJ: Therapy of cancer metastasis by tumoricidal activation of tissue macrophages using liposome-encapsulated immunomodulators. Pharmacol Ther. 78:141–154. 1998. View Article : Google Scholar : PubMed/NCBI
4	Sheridan C: Industry pursues co-stimulatory receptor immunomodulators to treat cancer. Nat Biotechnol. 31:181–183. 2013. View Article : Google Scholar : PubMed/NCBI
5	Berinstein NL: Enhancing cancer vaccines with immunomodulators. Vaccine. 25:(Suppl 2). B72–B88. 2007. View Article : Google Scholar : PubMed/NCBI
6	Yun TK: Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci. 16:Suppl. S3–S5. 2001. View Article : Google Scholar : PubMed/NCBI
7	Wu H, Chen J, Wang Q, Jia X, Song S, Yuan P, Liu K, Liu L, Zhang Y, Zhou A and Wei W: Ginsenoside metabolite compound K attenuates inflammatory responses of adjuvant-induced arthritis rats. Immunopharmacol Immunotoxicol. 36:124–129. 2014. View Article : Google Scholar : PubMed/NCBI
8	Liu KK, Wang QT, Yang SM, Chen JY, Wu HX and Wei W: Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis. Acta Pharmacol Sin. 35:599–612. 2014. View Article : Google Scholar : PubMed/NCBI
9	Chen J, Wu H, Wang Q, Chang Y, Liu K, Song S, Yuan P, Fu J, Sun W, Huang Q, et al: Ginsenoside metabolite compound k alleviates adjuvant-induced arthritis by suppressing T cell activation. Inflammation. 37:1608–1615. 2014. View Article : Google Scholar : PubMed/NCBI
10	Zhang Q, Hong B, Wu S and Niu T: Inhibition of prostatic cancer growth by ginsenoside Rh2. Tumour Biol. 36:2377–2381. 2015. View Article : Google Scholar : PubMed/NCBI
11	Shi Q, Li J, Feng Z, Zhao L, Luo L, You Z, Li D, Xia J, Zuo G and Chen D: Effect of ginsenoside Rh2 on the migratory ability of HepG2 liver carcinoma cells: Recruiting histone deacetylase and inhibiting activator protein 1 transcription factors. Mol Med Rep. 10:1779–1785. 2014.PubMed/NCBI
12	Tang XP, Tang GD, Fang CY, Liang ZH and Zhang LY: Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells. World J Gastroenterol. 19:1582–1592. 2013. View Article : Google Scholar : PubMed/NCBI
13	Zhou DB, Hu CP, Liang S and Yang HZ: Effect of ginsenoside Rh2 on immunocompetence of alveolar macrophages in patients with non-small cell lung cancer. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 32:868–872. 2007.(In Chinese). PubMed/NCBI
14	Wu R, Ru Q, Chen L, Ma B and Li C: Stereospecificity of ginsenoside Rg3 in the promotion of cellular immunity in hepatoma H22-bearing mice. J Food Sci. 79:H1430–H1435. 2014. View Article : Google Scholar : PubMed/NCBI
15	Waitz R, Solomon SB, Petre EN, Trumble AE, Fassò M, Norton L and Allison JP: Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy. Cancer Res. 72:430–439. 2012. View Article : Google Scholar : PubMed/NCBI
16	Li F, Guo Z, Yu H, Zhang X, Si T, Liu C, Yang X and Qi L: Anti-tumor immunological response induced by cryoablation and anti-CTLA-4 antibody in an in vivo RM-1 cell prostate cancer murine model. Neoplasma. 61:659–671. 2014. View Article : Google Scholar : PubMed/NCBI
17	Kvistborg P, Philips D, Kelderman S, Hageman L, Ottensmeier C, Joseph-Pietras D, Welters MJ, van der Burg S, Kapiteijn E, Michielin O, et al: Anti-CTLA-4 therapy broadens the melanoma-reactive CD8⁺ T cell response. Sci Transl Med. 6:254ra128. 2014. View Article : Google Scholar : PubMed/NCBI
18	Zhao Q, Tong L, He N, Feng G, Leng L, Sun W, Xu Y, Wang Y, Xiang R and Li Z: IFN-gamma mediates graft-versus-breast cancer effects via enhancing cytotoxic T lymphocyte activity. Exp Ther Med. 8:347–354. 2014.PubMed/NCBI
19	Gu Y, Wang GJ, Sun JG, Jia YW, Wang W, Xu MJ, Lv T, Zheng YT and Sai Y: Pharmacokinetic characterization of ginsenoside Rh2, an anticancer nutrient from ginseng, in rats and dogs. Food Chem Toxicol. 47:2257–2268. 2009. View Article : Google Scholar : PubMed/NCBI
20	Li S, Guo W, Gao Y and Liu Y: Ginsenoside Rh2 inhibits growth of glioblastoma multiforme through mTor. Tumour Biol. 36:6207–2612. 2015.
21	Li B, Zhao J, Wang CZ, Searle J, He TC, Yuan CS and Du W: Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett. 301:185–192. 2011. View Article : Google Scholar : PubMed/NCBI
22	Lee JH and Han Y: Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4⁺ T cell. Int Immunopharmacol. 6:1424–1430. 2006. View Article : Google Scholar : PubMed/NCBI
23	Lee EJ, Ko E, Lee J, Rho S, Ko S, Shin MK, Min BI, Hong MC, Kim SY and Bae H: Ginsenoside Rg1 enhances CD4(+) T-cell activities and modulates Th1/Th2 differentiation. Int ImmunoPharmacol. 4:235–244. 2004. View Article : Google Scholar : PubMed/NCBI
24	Yang Z, Chen A, Sun H, Ye Y and Fang W: Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice. Vaccine. 25:161–169. 2007. View Article : Google Scholar : PubMed/NCBI
25	Wang Y, Liu Y, Zhang XY, Xu LH, Ouyang DY, Liu KP, Pan H, He J and He XH: Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways. Int Immunopharmacol. 23:77–84. 2014. View Article : Google Scholar : PubMed/NCBI