Ginsenoside Rg1 attenuates invasion and migration by inhibiting transforming growth factor-β1-induced epithelial to mesenchymal transition in HepG2 cells

Yu,Meiling; Yu,Xiaobing; Guo,Daohua; Yu,Binbin; Li,Li; Liao,Qiao; Xing,Rong

doi:10.3892/mmr.2014.3098

Ginsenoside Rg1 attenuates invasion and migration by inhibiting transforming growth factor-β1-induced epithelial to mesenchymal transition in HepG2 cells

Authors:
- Meiling Yu
- Xiaobing Yu
- Daohua Guo
- Binbin Yu
- Li Li
- Qiao Liao
- Rong Xing
View Affiliations

Affiliations: Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Anhui, Bengbu 233004, P.R. China, Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Faculty of Pharmacy, Bengbu Medical College, Anhui, Bengbu 233030, P.R. China
Published online on: December 16, 2014 https://doi.org/10.3892/mmr.2014.3098
Pages: 3167-3173

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

Ginseng has become one of the most commonly used alternative herbal medicines and its active component, ginsenoside Rg1, possesses known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have not been investigated. The present study demonstrated that ginsenoside Rg1 was able to suppress transforming growth factor‑β1 (TGF‑β1)‑induced invasion and migration in HepG2 liver cancer cells. This suppression was associated with the inhibition of TGF‑β1‑induced epithelial to mesenchymal transition (EMT). Furthermore, TGF‑β1 induced HepG2 cells to undergo EMT and significantly promoted cell invasion and migration. When cells were pretreated with ginsenoside Rg1 for 24 h and subsequently exposed to TGF‑β1 for 24 h, the results demonstrated that ginsenoside Rg1 inhibited the initiation of TGF‑β1‑induced EMT. In addition, HepG2 cells exhibited a mesenchymal phenotype when exposed to TGF‑β1, but when exposed to ginsenoside Rg1 this effect was reversed and the cells exhibited a classical epithelial morphology. Ginsenoside Rg1 also increased the expression of the epithelial phenotype marker E‑cadherin and repressed the expression of the mesenchymal phenotype marker vimentin. In conclusion, the results of the present study suggest that ginsenoside Rg1 may suppress liver cancer invasion and migration in vitro through inhibiting TGF‑β1‑induced EMT.

View Figures

View References

1	Jemal A, Murray T, Ward E, et al: Cancer statistics, 2005. CA Cancer J Clin. 55:10–30. 2005. View Article : Google Scholar : PubMed/NCBI
2	Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2011. View Article : Google Scholar : PubMed/NCBI
3	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
4	Chang CJ, Chao CH, Xia W, et al: P53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol. 13:317–323. 2011. View Article : Google Scholar : PubMed/NCBI
5	Thiery JP, Acloque H, Huang RY, et al: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
6	Voulgari A and Pintzas A: Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 1796:75–90. 2009.PubMed/NCBI
7	Lee JM, Dedhar S, Kalluri R, et al: The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 172:973–981. 2006. View Article : Google Scholar : PubMed/NCBI
8	Zavadil J and Böttinger EP: TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 24:5764–5774. 2005. View Article : Google Scholar : PubMed/NCBI
9	Yang J and Weinberg RA: Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 14:818–829. 2008. View Article : Google Scholar : PubMed/NCBI
10	Attele AS, Wu JA and Yuan CS: Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 58:1685–1693. 1999. View Article : Google Scholar : PubMed/NCBI
11	Lee EJ, Ko E, Lee J, et al: Ginsenoside Rg1 enhances CD4(+) T-cell activities and modulates Th1/Th2 differentiation. Int Immunopharmacol. 4:235–244. 2004. View Article : Google Scholar : PubMed/NCBI
12	Li CY, Deng W, Liao XQ, et al: The effects and mechanism of ginsenoside Rg1 on myocardial remodeling in an animal model of chronic thromboembolic pulmonary hypertension. Eur J Med Res. 18:162013. View Article : Google Scholar : PubMed/NCBI
13	Li QF, Shi SL, Liu QR, et al: Anticancer effects of ginsenoside Rg1, cinnamic acid, and tanshinone IIA in osteosarcoma MG-63 cells: nuclear matrix downregulation and cytoplasmic trafficking of nucleophosmin. Int J Biochem Cell Biol. 40:1918–1929. 2008. View Article : Google Scholar : PubMed/NCBI
14	Liu J, Cai SZ, Zhou Y, et al: Senescence as a consequence of ginsenoside rg1 response on k562 human leukemia cell line. Asian Pac J Cancer Prev. 13:6191–6196. 2012. View Article : Google Scholar : PubMed/NCBI
15	Liu Q, Kou JP and Yu BY: Ginsenoside Rg1 protects against hydrogen peroxide-induced cell death in PC12 cells via inhibiting NF-κB activation. Neurochem Int. 58:119–125. 2011. View Article : Google Scholar
16	Qu DF, Yu HJ, Liu Z, et al: Ginsenoside Rg1 enhances immune response induced by recombinant Toxoplasma gondii SAG1 antigen. Vet Parasitol. 179:28–34. 2011. View Article : Google Scholar : PubMed/NCBI
17	Xu L, Chen WF and Wong MS: Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson’s disease through the IGF-I receptor signalling pathway. Br J Pharmacol. 158:738–748. 2009. View Article : Google Scholar : PubMed/NCBI
18	Li L, Wang Y, Qi B, et al: Suppression of PMA-induced tumor cell invasion and migration by ginsenoside Rg1 via the inhibition of NF-κB-dependent MMP-9 expression. Oncol Rep. 32:1779–1786. 2014.PubMed/NCBI
19	Ellenrieder V, Hendler SF, Boeck W, et al: Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res. 61:4222–4228. 2001.PubMed/NCBI
20	Chen J, Li Q, An Y, et al: CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer. Int J Oncol. 43:877–885. 2013.PubMed/NCBI
21	Creighton CJ, Gibbons DL and Kurie JM: The role of epithelial-mesenchymal transition programming in invasion and metastasis: a clinical perspective. Cancer Manag Res. 5:187–195. 2013. View Article : Google Scholar : PubMed/NCBI
22	Polyak K and Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 9:265–273. 2009. View Article : Google Scholar : PubMed/NCBI
23	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
24	Nagai T, Arao T, Furuta K, et al: Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma. Mol Cancer Ther. 10:169–177. 2011. View Article : Google Scholar : PubMed/NCBI
25	Shin JA, Hong OK, Lee HJ, et al: Transforming growth factor-β induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells. J Cell Biochem. 112:179–188. 2011. View Article : Google Scholar
26	Yang JJ, Lim JY, Huang J, et al: The role of inherited TPMT and COMT genetic variation in cisplatin-induced ototoxicity in children with cancer. Clin Pharmacol Ther. 94:252–259. 2013. View Article : Google Scholar : PubMed/NCBI
27	Li J, Wei Q, Zuo GW, et al: Ginsenoside Rg1 induces apoptosis through inhibition of the EpoR-mediated JAK2/STAT5 signalling pathway in the TF-1/Epo human leukemia cell line. Asian Pac J Cancer Prev. 15:2453–9. 2014. View Article : Google Scholar