Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression.
Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression.
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人参皂苷 Rg3 诱导 EGFR/MAPK 通路失活通过降低 FUT4/LeY 表达抑制黑色素瘤细胞增殖
DOI：
10.3892/ijo.2015.2886
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发表时间：
2015-04
影响因子：
5.2
通讯作者：
Liu JW
中科院分区：
文献类型：
--
作者：
Shan X;Aziz F;Tian LL;Wang XQ;Yan Q;Liu JW
恶性黑色素瘤是一种具有破坏性和致命性的皮肤癌，预后不良。非常需要一种有效的黑色素瘤治疗方法。人参皂苷Rg 3是一种具有抗肿瘤活性的中草药。研究发现糖基化异常与肿瘤细胞生长密切相关。然而，Rg 3对黑色素瘤的抗肿瘤作用及其调节糖基化的机制尚不清楚。我们发现Rg 3不仅以剂量依赖的方式抑制A375黑色素瘤细胞增殖，而且还降低岩藻糖基转移酶IV（FUT 4）及其合成产物刘易斯Y（LeY）（一种肿瘤相关糖抗原（TACA））的表达。siRNA敲低FUT 4表达后，FUT 4/LeY水平显著降低，并通过抑制EGFR/MAPK通路的激活抑制细胞增殖。一致地，在异种移植黑素瘤小鼠模型中也观察到Rg 3和FUT 4敲低对黑素瘤生长的抑制作用。总之，Rg 3通过下调FUT 4在体外和体内有效地抑制黑色素瘤细胞的生长。通过Rg 3靶向FUT 4/LeY介导的岩藻糖基化，抑制EGFR/MAPK通路的激活，并阻止黑色素瘤生长。这项研究的结果表明，Rg 3是一种潜在的新的治疗黑色素瘤的治疗剂。
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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影响因子：
5.6
作者：
Wang Y;Liu J;Lin B;Wang C;Li Q;Liu S;Yan L;Zhang S;Iwamori M
通讯作者：
Iwamori M
DOI：
10.1016/j.bbagen.2004.03.006
发表时间：
2004-06-11
影响因子：
3
作者：
Azuma, Y;Ito, M;Matsumoto, K
通讯作者：
Matsumoto, K
CD147和Lewis y抗原在卵巢癌中的表达及其与耐药的关系
影响因子：
3.4
作者：
Gao, Jian;Hu, Zhenhua;Lin, Bei
通讯作者：
Lin, Bei
影响因子：
6.3
作者：
通讯作者：
--
影响因子：
3.6
作者：
Kim, Jae-Won;Jung, Seok-Yun;Kwon, Sang-Mo
通讯作者：
Kwon, Sang-Mo