Oncotarget

Research Papers:

OSU-A9 inhibits pancreatic cancer cell lines by modulating p38-JAK-STAT3 signaling

Wan-Chi Tsai, Li-Yuan Bai, Yi-Jin Chen, Po-Chen Chu, Ya-Wen Hsu, Aaron M. Sargeant and Jing-Ru Weng _

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Oncotarget. 2017; 8:29233-29246. https://doi.org/10.18632/oncotarget.16450

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Abstract

Wan-Chi Tsai1,2, Li-Yuan Bai3,4, Yi-Jin Chen1, Po-Chen Chu5,6, Ya-Wen Hsu7, Aaron M. Sargeant8, Jing-Ru Weng9

1Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

2Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

3College of Medicine, China Medical University, Taichung 40402, Taiwan

4Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan

5Institute of Biological Chemistry, Academia Sinica, Taipei 11574, Taiwan

6Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan

7Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan 71745, Taiwan

8Charles River Laboratories, Safety Assessment, Spencerville, OH 45887, USA

9Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan

Correspondence to:

Jing-Ru Weng, email: columnster@gmail.com

Keywords: OSU-A9, pancreatic cancer, p38, JAK, STAT3

Received: January 05, 2016     Accepted: February 27, 2017     Published: March 22, 2017

ABSTRACT

Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of death worldwide. Since there is a dire need for novel and effective therapies to improve the poor survival rates of advanced pancreatic cancer patients, we analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger antitumor effect than gemcitabine on two pancreatic cancer cell lines, including gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down-regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and decreased phosphorylation of JAK and STAT3. Cell migration and invasiveness assays showed that OSU-A9 reduced cancer cell aggressiveness and inhibited BxPC-3 xenograft growth in nude mice. These results suggest that OSU-A9 modulates the p38-JAK-STAT3 signaling module, thereby inducing cytotoxicity in pancreatic cancer cells. Continued evaluation of OSU-A9 as a potential therapeutic agent for pancreatic cancer thus appears warrented.


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