Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer

被引：13

作者：

Prajapati, Dipakkumar R. ^{[1
]}

Molczyk, Caitlin ^{[1
]}

Purohit, Abhilasha ^{[1
]}

Saxena, Sugandha ^{[1
]}

Sturgeon, Reegan ^{[1
]}

Dave, Bhavana J. ^{[1
]}

Kumar, Sushil ^{[2
]}

Batra, Surinder K. ^{[2
]}

Singh, Rakesh K. ^{[1
]}

机构：

[1] Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA

来源：

CANCER LETTERS | 2023年 / 563卷

基金：

美国国家卫生研究院;

关键词：

Pancreatic cancer; CXCR2; antagonist; Tumor growth; Angiogenesis; Neutrophils; Metastasis; DIFFERENTIAL EXPRESSION; COLON-CANCER; CELLS; SURVIVAL; PROLIFERATION; RECEPTOR; POTENT; CHEMORESISTANCE; OVEREXPRESSION; RESPONSIVENESS;

D O I：

10.1016/j.canlet.2023.216185

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic cancer (PC) has a poor prognosis, and current therapeutic strategies are ineffective in advanced diseases. We and others have shown the aberrant expression of CXCR2 and its ligands in PC development and progression. Our objective for this study was to evaluate the therapeutic utility of CXCR2/1 targeting using an small molecule antagonist, SCH-479833, in different PC preclinical murine models (syngeneic or xenogeneic). Our results demonstrate that CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Treatment with the antagonist enhanced fibrosis, tumor necrosis, and extramedullary hematopoiesis. Together, these findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis.

引用

页数：9

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