Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

Yuebo Zhang; Yong Ma; Ying Wang; Debabrata Mukhopadhyay; Yan Bi; Baoan Ji

doi:10.1016/j.pan.2022.03.019

Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

Yuebo Zhang, Yong Ma, Ying Wang, Debabrata Mukhopadhyay, Yan Bi, Baoan Ji

Research output: Contribution to journal › Article › peer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is notorious for high mortality due to limited options of appropriate chemotherapy drugs. Here we report that Aurora kinase-A expression is elevated in both human and mouse PDAC samples. MLN8237, an inhibitor of Aurora kinase-A, efficiently reduced the proliferation and motility of PDAC cells in vitro as well as tumor growth in orthotropic xenograft model and genetic pancreatic cancer animal models (p53/LSL/Pdx-Cre mice) in vivo. MLN8237 exhibited tumor inhibitory effect through inhibiting proliferation and migration, and inducing apoptosis and senescence. These results provide the molecular basis for a novel chemotherapy strategy for PDAC patients.

Original language	English (US)
Pages (from-to)	619-625
Number of pages	7
Journal	Pancreatology
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.pan.2022.03.019
State	Published - Jun 2022

Keywords

Apoptosis
Aurora kinase
Pancreatic cancer
Senescence
Xenograft

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Hepatology
Gastroenterology

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10.1016/j.pan.2022.03.019

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title = "Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) is notorious for high mortality due to limited options of appropriate chemotherapy drugs. Here we report that Aurora kinase-A expression is elevated in both human and mouse PDAC samples. MLN8237, an inhibitor of Aurora kinase-A, efficiently reduced the proliferation and motility of PDAC cells in vitro as well as tumor growth in orthotropic xenograft model and genetic pancreatic cancer animal models (p53/LSL/Pdx-Cre mice) in vivo. MLN8237 exhibited tumor inhibitory effect through inhibiting proliferation and migration, and inducing apoptosis and senescence. These results provide the molecular basis for a novel chemotherapy strategy for PDAC patients.",

keywords = "Apoptosis, Aurora kinase, Pancreatic cancer, Senescence, Xenograft",

author = "Yuebo Zhang and Yong Ma and Ying Wang and Debabrata Mukhopadhyay and Yan Bi and Baoan Ji",

note = "Funding Information: This work was supported by 5K12 CA090628-18, P50 CA102701 and NCI CA255068 . Publisher Copyright: {\textcopyright} 2022 IAP and EPC",

year = "2022",

month = jun,

doi = "10.1016/j.pan.2022.03.019",

language = "English (US)",

volume = "22",

pages = "619--625",

journal = "Pancreatology",

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TY - JOUR

T1 - Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

AU - Zhang, Yuebo

AU - Ma, Yong

AU - Wang, Ying

AU - Mukhopadhyay, Debabrata

AU - Bi, Yan

AU - Ji, Baoan

PY - 2022/6

Y1 - 2022/6

N2 - Pancreatic ductal adenocarcinoma (PDAC) is notorious for high mortality due to limited options of appropriate chemotherapy drugs. Here we report that Aurora kinase-A expression is elevated in both human and mouse PDAC samples. MLN8237, an inhibitor of Aurora kinase-A, efficiently reduced the proliferation and motility of PDAC cells in vitro as well as tumor growth in orthotropic xenograft model and genetic pancreatic cancer animal models (p53/LSL/Pdx-Cre mice) in vivo. MLN8237 exhibited tumor inhibitory effect through inhibiting proliferation and migration, and inducing apoptosis and senescence. These results provide the molecular basis for a novel chemotherapy strategy for PDAC patients.

AB - Pancreatic ductal adenocarcinoma (PDAC) is notorious for high mortality due to limited options of appropriate chemotherapy drugs. Here we report that Aurora kinase-A expression is elevated in both human and mouse PDAC samples. MLN8237, an inhibitor of Aurora kinase-A, efficiently reduced the proliferation and motility of PDAC cells in vitro as well as tumor growth in orthotropic xenograft model and genetic pancreatic cancer animal models (p53/LSL/Pdx-Cre mice) in vivo. MLN8237 exhibited tumor inhibitory effect through inhibiting proliferation and migration, and inducing apoptosis and senescence. These results provide the molecular basis for a novel chemotherapy strategy for PDAC patients.

KW - Apoptosis

KW - Aurora kinase

KW - Pancreatic cancer

KW - Senescence

KW - Xenograft

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JO - Pancreatology

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Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

Abstract

Keywords

ASJC Scopus subject areas

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