The molecular mechanisms of a novel multi-kinase inhibitor ZLJ33 in suppressing pancreatic cancer growth

被引：7

作者：

Li, Yan ^{[1
,2
,3
]}

Tang, Ke ^{[1
,2
,3
]}

Zhang, Lijing ^{[2
,4
,5
]}

Li, Chao ^{[1
,2
,3
]}

Niu, Fei ^{[1
,2
,3
]}

Zhou, Wanqi ^{[1
,2
,3
]}

Yang, Hanze ^{[1
,2
,3
]}

Feng, Zhiqiang ^{[2
,4
,5
]}

Chen, Xiaoguang ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, State Key Lab Bioact Subst & Funct Nat Med, Inst Mat Med, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Chinese Acad Med Sci, Dept Pharmacol, Inst Mat Med, Beijing 100050, Peoples R China

[4] Chinese Acad Med Sci, Beijing Key Lab Active Substance Discovery & Drug, Inst Mat Med, Beijing 100050, Peoples R China

[5] Chinese Acad Med Sci, Dept Pharmacochem, Inst Mat Med, Beijing 100050, Peoples R China

来源：

CANCER LETTERS | 2015年 / 356卷 / 02期

关键词：

Multi-kinase inhibitor; Pancreatic cancer; Antiproliferation; PDGFR beta; RET; c-Raf; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; RAF/MEK/ERK PATHWAY; RAS/RAF/MEK/ERK PATHWAY; MULTIKINASE INHIBITOR; CELL-PROLIFERATION; SIGNALING PATHWAYS; FACTOR RECEPTOR; ACTIVATED AKT; EXPRESSION; SORAFENIB;

D O I：

10.1016/j.canlet.2014.09.040

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

ZLJ33, an oral active multi-kinase inhibitor, was evaluated both in vitro and in vivo against human pancreatic cancer. It could effectively inhibit cell proliferation, induce apoptosis, and cause inhibition of invasion in pancreatic cancer cells. At a dose of 15.0 mg/kg, ZLJ33 induced tumor shrink in Mia-PaCa2, Capan2, and AsPC-1 xenografts models by 60.59%, 74.19%, and 71.54% according to the tumor weight, respectively. The effect of ZLJ33 on pancreatic cancer was mainly mediated by inactivation of p-PDGFR beta, p-c-Raf, and p-RET. Treatment with ZLJ33 did not cause side effect of hematology indexes in the pancreatic cancer xenograft model. ZLJ33 could be a potential therapeutic agent against pancreatic cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：392 / 403

页数：12

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