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Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells

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Tumor Biology

Abstract

Zoledronate (ZOL) is a third-generation bisphosphonate (BP), clinically used to treat lytic bone lesions caused by malignancies or bone resorption disorders. Mechanistically, ZOL was recently shown to have direct pro-apoptotic effects on tumor cells and to inhibit cancer cell invasion, adhesion, proliferation, and angiogenesis. The molecular mechanism of ZOL-induced apoptosis remains unknown. In this study, we observed that ZOL induced apoptosis in colorectal cancer cells HCT116 and Caco-2. After HCT116 and Caco-2 cells were treated with ZOL, decreased fluorescence of JC-1 aggregates (590 nm) was seen in mitochondria. Western blotting analysis showed that cytochrome c was decreased in the mitochondria and increased in the cytosol, respectively. The effects were dependent on the concentration and treatment time by ZOL. In vivo experiments showed that ZOL inhibited the growth of xenograft tumor in mice. Hematoxylin and eosin (H&E) staining of tissue samples showed a significantly increased apoptosis body in the ZOL-treated xenografts compared to control. Taken together, our data demonstrated that ZOL inhibits growth of HCT116 cells both in vitro and in vivo and induce apoptosis through the mitochondria pathway.

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Acknowledgments

This study was supported by grants from the Wuxi hospital administrative center and Wuxi Science and Technology Bureau (YGM1109, YGZ1108, CSE31N1314)

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    Authors and Affiliations

    1. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

      Xiang Gao & Weichang Chen

    2. Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, 214062, China

      Bo Jiang, Xiaosong Ge & Dong Hua

    3. Wuxi Cancer Institute & Affiliated Hospital of Jiangnan University, Wuxi, 214062, China

      Bo Jiang, Shitao Zou & Ting Zhang

    4. Department of pathology, Affiliated Hospital of Jiangnan University, Wuxi, 214062, China

      Xiaowei Qi & Linfang Jin

    5. Georgia Regents University Cancer Center, 1411 Laney Walker Blvd, Augusta, GA, 30912, USA

      Shou-Ching Tang

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    1. Xiang Gao
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    Correspondence to Weichang Chen.

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    Xiang Gao and Bo Jiang contributed equally to this work.

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    Gao, X., Jiang, B., Zou, S. et al. Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells. Tumor Biol. 36, 5315–5322 (2015). https://doi.org/10.1007/s13277-015-3192-x

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    • DOI: https://doi.org/10.1007/s13277-015-3192-x

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