Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression

Shan,Xiu; Aziz,Faisal; Tian,Li Li; Wang,Xiao Qi; Yan,Qiu; Liu,Ji Wei

doi:10.3892/ijo.2015.2886

Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression

Authors:
- Xiu Shan
- Faisal Aziz
- Li Li Tian
- Xiao Qi Wang
- Qiu Yan
- Ji Wei Liu
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Affiliations: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China, Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, Liaoning, P.R. China, Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA
Published online on: February 10, 2015 https://doi.org/10.3892/ijo.2015.2886
Pages: 1667-1676

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Abstract

Malignant melanoma is a destructive and lethal form of skin cancer with poor prognosis. An effective treatment for melanoma is greatly needed. Ginsenoside Rg3 is a herbal medicine with high antitumor activity. It is reported that abnormal glycosylation is correlated with the tumor cell growth. However, the antitumor effect of Rg3 on melanoma and its mechanism on regulating glycosylation are unknown. We found that Rg3 did not only inhibit A375 melanoma cell proliferation in a dose-dependent manner, but also decreased the expression of fucosyltransferase IV (FUT4) and its synthetic product Lewis Y (LeY), a tumor-associated carbohydrate antigen (TACA). Knocking down FUT4 expression by siRNA dramatically reduced FUT4/LeY level and inhibited cell proliferation through preventing the activation of EGFR/MAPK pathway. Consistently, the inhibitory effect of the Rg3 and FUT4 knockdown on melanoma growth was also seen in a xenograft melanoma mouse model. In conclusion, Rg3 effectively inhibited melanoma cell growth by downregulating FUT4 both in vitro and in vivo. Targeting FUT4/LeY mediated fucosylation by Rg3 inhibited the activation of EGFR/MAPK pathway and prevented melanoma growth. Results from this study suggest Rg3 is a potential novel therapy agent for melanoma treatment.

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