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Secreted protein acidic and rich in cysteine enhances the chemosensitivity of pancreatic cancer cells to gemcitabine

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Tumor Biology

Abstract

It has been previously shown that the simultaneous exposure of colon cancer cells MIP to irinotecan and secreted protein acidic and rich in cysteine (SPARC) enhances anticancer activity. However, whether there is same effect of SPARC in pancreatic cancer remains largely unknown. Therefore in this study, we aimed to investigate the role of SPARC played in the sensitivity of pancreatic cancer to gemcitabine. We first treated MIAPaCa2 and MIAPaCa2/SPARC69 cells with different concentrations of gemcitabine (2, 5, 10, and 20 μM) for 24, 48, and 72 h and selected the appropriated concentration for further study. Then we analyzed cell viability, cell cycle, and apoptosis and the levels of apoptosis-related proteins by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting and Western blot were used, respectively. In this study, we found that gemcitabine inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Overexpression of SPARC increased the inhibiting effect of gemcitabine on pancreatic cancer cells. The colony size of MIAPaCa2/SPARC69 was much smaller than that of MIAPaCa2/V. There was a G0/G1 arrest with significant increase of apoptosis after gemcitabine treatment in MIAPaCa2/SPARC69 cells. Furthermore, our results demonstrated that overexpression of SPARC markedly increased the levels of pro-apoptotic proteins in gemcitabine-treated pancreatic cancer cells. The SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins. These results have shown that the SPARC/ gemcitabine combination treatment may be a potentially useful therapeutic option for individuals diagnosed with pancreatic cancer

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Acknowledgments

The authors would like to thank Dr. Shi Lei (Chi Biotechnology) for critical reading. This work was sponsored by The natural science foundation of Jiangsu Province (Youth Fund), grant number BK20130475; Zhenjiang Science and Technology Pillar Program, grant numbers SH2012030, SH2012031, and SH2014035; The Foundation for Young Scientists of affiliated Hospital of Jiangsu University (grant number JDFYRC2013009); post-doctoral research funding schemes of Jiangsu Province (grant number 1302096B); and Research innovation project of Jiangsu Province General University Graduate (CXLX13-688).

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    Authors and Affiliations

    1. Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People’s Republic of China

      Xin Fan, Zhengfa Mao, Lei Cui, Jianguo Qu, ShengChun Dang, Xuqing Wang & Jianxin Zhang

    2. Department of Gynecology and Obstetrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People’s Republic of China

      Xiaoyan Ma

    3. Department of Senior officer’s Health Care, Nanjing General Hospital of Nanjing Military Area Command, Nanjing, Jiangsu Province, People’s Republic of China

      Lihui Lv

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    1. Xin Fan
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    Correspondence to Jianxin Zhang.

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    Xin Fan and Zhengfa Mao contributed equally to this work.

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    Fan, X., Mao, Z., Ma, X. et al. Secreted protein acidic and rich in cysteine enhances the chemosensitivity of pancreatic cancer cells to gemcitabine. Tumor Biol. 37, 2267–2273 (2016). https://doi.org/10.1007/s13277-015-4044-4

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    • DOI: https://doi.org/10.1007/s13277-015-4044-4

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