Anticancer Effect of Ginsenoside Rg3 on Mice Colorectal Cancer_West China Medical Journal

Authors：

 NIEShi-hong ¹ , ZANGJian ² , CAODan ¹ , LIUTai-guo ¹ ,  YICheng ¹

1. Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Radiation Oncology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, P. R. China;

Corresponding?author：

YICheng, Email: yicheng6834@163.com

Keywords：

Ginsenoside Rg3; Colorectal cancer; Tumor necrosis; Mice

DOI：

10.7507/1002-0179.20150122

Video：

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Objective To observe the anticancer efficacy of ginsenoside Rg3 on colorectal cancer in vitro and in vivo. Methods Mice colorectal cell line (CT26) was incubated in 96-well plates (3×10³-4×10³ per well) with various concentrations of ginsenoside Rg3 (0, 5, 10, 15, 20 μg/mL) for 24 hours and 48 hours. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-dipheny 1-2-H-tetrazolium bromide assay was used to detect the inhibitory rate of cells. Xenograft models were established by subcutaneous implantation of CT26 cells into BABL/c mice. Each mouse was injected with 1×10⁷ cells suspended in serum-free medium. Xenograft mice were randomized into four groups: physiological saline group, ginsenoside Rg3 5 mg/kg group, ginsenoside Rg3 10 mg/kg group, and ginsenoside Rg3 20 mg/kg group. Ginsenoside Rg3 was administrated to mice by intragastric gavage. All animals were observed for activity, body weight, tumor size, survival time, mental state and adverse effect of ginsenoside Rg3. Hematoxylin-eosin stain was used for comparing necrosis rate among groups. Results The inhibitory rates of cells were increasing following the elevating concentrations of ginsenoside Rg3. The anti-proliferation effect of ginsenoside Rg3 for 48 hours was weaker than the anti-proliferation effect for 24 hours. The decrease of mice body weight was slower than physiological saline group after administration of ginsenoside Rg3, and the number of mice with worse physiological state, lack of activity and loss of appetite in physiological saline group were more than that in ginsenoside Rg3 groups. However, these results among four groups were not significantly different (P>0.05). There were no obvious adverse effects of ginsenoside Rg3 found during the whole study. The necrosis rate of physiological saline group, Rg3 10 mg/kg group and Rg3 20 mg/kg group was 20%, 60% and 80% respectively. Conclusion Ginsenoside Rg3, as a single agent, still has anticancer activity. The anticancer efficacy is increasing following the elevating concentrations of ginsenoside Rg3. Ginsenoside Rg3 is a dose dependent agent.

Citation： NIEShi-hong, ZANGJian, CAODan, LIUTai-guo, YICheng. Anticancer Effect of Ginsenoside Rg3 on Mice Colorectal Cancer. West China Medical Journal, 2015, 30(3): 411-416. doi: 10.7507/1002-0179.20150122 Copy

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10.	Lee SY, Kim GT, Roh SH, et al. Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines[J]. Biosci Biotechnol Biochem, 2009,73(4):811-816.
11.	Wang CZ, Xie JT, Fishbein A, et al. Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells[J]. Phytother Res, 2009, 23(1):6-13.
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15.	Kim SM, Lee SY, Yuk DY, et al. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel[J]. Arch Pharm Res, 2009, 32(5):755-765.

1. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase Ⅲ trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer:the PRIME study[J]. J Clin Oncol, 2010, 28(31):4697-4705.
2. Peeters M, Price TJ, Cervantes A, et al. Randomized phase Ⅲ study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer[J]. J Clin Oncol, 2010, 28(31):4706-4713.
3. Hendlisz A, Van Den Eynde M, Peeters M, et al. Phase Ⅲ trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy[J]. J Clin Oncol, 2010, 28(23):3687-3694.
4. Tebbutt NC, Wilson K, Gebski VJ, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer:results of the Australasian Gastrointestinal Trials Group Randomized Phase Ⅲ MAX Study[J]. J Clin Oncol, 2010, 28(19):3191-3198.
5. Khambata-Ford S, Harbison CT, Hart LL, et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase Ⅲ study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer[J]. J Clin Oncol, 2010, 28(6):918-927.
6. 陳俊霞, 俊夏, 劉基巍, 等. 人參皂甙Rg3誘導乳腺癌細胞系MCF-7凋亡的實驗研究[J]. 癌變·畸變·突變, 2005, 17(4):213-216.
7. 何芳, 曾文鋌, 沈浩賢. 人參皂甙Rg3聯合三氧化二砷對人肝癌裸鼠的治療作用[J]. 中國誤診學雜志, 2007, 7(28):6757-6758.
8. 孫燕, 林洪生, 朱允中, 等. 長春瑞濱合并順鉑(NP)加參一膠囊或安慰劑治療晚期非小細胞肺癌的多中心雙盲隨機臨床研究報告[J]. 中國肺癌雜志, 2006, 9(3):254-258.
9. Chen J, Peng H, Ou-Yang X, et al. Research on the antitumor effect of ginsenoside Rg3 in B16 melanoma cells[J]. Melanoma Res, 2008, 18(5):322-329.
10. Lee SY, Kim GT, Roh SH, et al. Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines[J]. Biosci Biotechnol Biochem, 2009,73(4):811-816.
11. Wang CZ, Xie JT, Fishbein A, et al. Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells[J]. Phytother Res, 2009, 23(1):6-13.
12. Li B, Zhao J, Wang CZ, et al. Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53[J]. Cancer Lett, 2011, 301(2):185-192.
13. Liu TG, Huang Y, Cui DD, et al. Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice[J]. BMC Cancer, 2009, 9:250.
14. Xu TM, Xin Y, Cui MH, et al. Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer[J]. Chin Med J, 2007, 120(7):584-588.
15. Kim SM, Lee SY, Yuk DY, et al. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel[J]. Arch Pharm Res, 2009, 32(5):755-765.

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