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Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic cancer

Tumor Biology

Abstract

Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas. However, whether periostin contributed to chemoresistance in PDAC remains unknown. Therefore, we focused on the role of periostin in PDAC by observing the effects of silencing this gene on gemcitabine resistance in vitro and in vivo aiming to explore the possible molecular mechanism. In this study, the pancreatic cancer cell (PCC) proliferation and apoptosis were assayed to investigate the sensitivity to gemcitabine after silencing periostin. We provide the evidence that periostin not only drives the carcinogenic process itself but also significantly associated with gemcitabine-induced apoptosis. These findings collectively indicated that periostin increases the chemoresistance to gemcitabine. Thus, targeting periostin might offer a new opportunity to overcome the gemcitabine resistance of PDAC.

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Acknowledgments

We would like to acknowledge the funding support from the National Natural Science Foundation of China (Nos. 81271596, Nos. 81571679, and Nos. 81471666) and the Medical and Engineering Cross-Foundation of Shanghai Jiaotong University (Nos. YG2015ZD09). We also gratefully acknowledge the entire staff of the Department of Pathophysiology in the Key Laboratory of Cell Differentiation and Apoptosis of the National Ministry of Education.

Author contributions

Y. Liu, F. Li, F. Gao, L. X. Xing, and P. Qin performed the experiments. Y. Liu, F. Li, Q. Zhao, L. F. Du, X. X. Liang, J. J. Zhang, X. H. Qiao, and L. Z. Lin planned the experiments, analyzed the data, and interpreted the results. Y. Liu and F. Li wrote the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China

    Yang Liu, Fan Li, Feng Gao, Lingxi Xing, Xingxin Liang, Jiajie Zhang, Xiaohui Qiao, Lizhou Lin & Lianfang Du

  2. Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China

    Peng Qin

  3. Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis and National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China

    Qian Zhao

Authors
  1. Yang Liu
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  2. Fan Li
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  3. Feng Gao
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  4. Lingxi Xing
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  5. Peng Qin
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  6. Xingxin Liang
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  7. Jiajie Zhang
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  8. Xiaohui Qiao
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  9. Lizhou Lin
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  10. Qian Zhao
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  11. Lianfang Du
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Corresponding authors

Correspondence to Qian Zhao or Lianfang Du.

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Ethical statement

Informed consent was obtained from all participants and this research was approved by the ethics committee of Shanghai General Hospital affiliated of Shanghai Jiaotong University and performed in accordance with ethical principles. The experiments were undertaken with the understanding and written consent of each subject. All mouse experiments were performed according to the protocols approved by Shanghai Medical Experimental Animal Care Commission.

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Additional information

Yang Liu and Fan Li contributed equally in this manuscript.

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Liu, Y., Li, F., Gao, F. et al. Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic cancer. Tumor Biol. 37, 15283–15291 (2016). https://doi.org/10.1007/s13277-016-5321-6

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  • DOI: https://doi.org/10.1007/s13277-016-5321-6

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