Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway

被引：21

作者：

Zhang, Mingdi ^{[1
,2
]}

Cai, Shizhong ^{[3
]}

Zuo, Bin ^{[4
]}

Gong, Wei ^{[1
]}

Tang, Zhaohui ^{[1
]}

Zhou, Di ^{[1
]}

Weng, Mingzhe ^{[1
]}

Qin, Yiyu ^{[1
]}

Wang, Shouhua ^{[1
]}

Liu, Jun ^{[5
]}

Ma, Fei ^{[6
]}

Quan, Zhiwei ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

[2] Fudan Univ, Shanghai Gynecol Hosp, Dept Breast Surg, Shanghai, Peoples R China

[3] Soochow Univ, Childrens Hosp, Dept Child & Adolescent Healthcare, Suzhou, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Orthoped Surg, Shanghai, Peoples R China

[5] Soochow Univ, Affiliated Hosp 1, Minist Hlth,Collaborat Innovat Ctr Haematol, Jiangsu Inst Haematol,Key Lab Thrombosis & Haemos, Suzhou, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Oncol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

来源：

TUMOR BIOLOGY | 2017年 / 39卷 / 05期

关键词：

Senescence; gallbladder cancer; arctigenin; epidermal growth factor receptor; CELL-CYCLE ARREST; SIGNALING PATHWAY; BILIARY CANCER; PHASE-II; APOPTOSIS; EXPRESSION; MUTATIONS; CARCINOMA; ERLOTINIB; MULTICENTER;

D O I：

10.1177/1010428317698359

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

引用

页数：15

共 43 条

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