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Significantly inhibitory effects of low molecular weight heparin (Fraxiparine) on the motility of lung cancer cells and its related mechanism

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Tumor Biology

Abstract

Low molecular weight heparin (LMWH) improving the cancer survival has been attracting attention for many years. Our previous study found that LMWH (Fraxiparine) strongly downregulated the invasive, migratory, and adhesive ability of human lung adenocarcinoma A549 cells. Here, we aimed to further identify the antitumor effects and possible mechanisms of Fraxiparine on A549 cells and human highly metastatic lung cancer 95D cells. The ability of cell invasion, migration, and adhesion were measured by Transwell, Millicell, and MTT assays. FITC-labeled phalloidin was used to detect F-actin bundles in cells. Chemotactic migration was analyzed in a modified Transwell assay. Measurement of protein expression and phosphorylation activity of PI3K, Akt, and mTOR was performed with Western blot. Our studies found that Fraxiparine significantly inhibited the invasive, migratory, and adhesive characteristics of A549 and 95D cells after 24 h incubation and showed a dose-dependent manner. Fraxiparine influenced the actin cytoskeleton rearrangement of A549 and 95D cells by preventing F-actin polymerization. Moreover, Fraxiparine could significantly inhibit CXCL12-mediated chemotactic migration of A549 and 95D cells in a concentration-dependent manner. Furthermore, Fraxiparine might destroy the interaction between CXCL12-CXCR4 axis, then suppress the PI3K-Akt-mTOR signaling pathway in lung cancer cells. For the first time, our data indicated that Fraxiparine could significantly inhibit the motility of lung cancer cells by restraining the actin cytoskeleton reorganization, and its related mechanism might be through inhibiting PI3K-Akt-mTOR signaling pathway mediated by CXCL12-CXCR4 axis. Therefore, Fraxiparine would be a potential drug for lung cancer metastasis therapy.

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Acknowledgments

This project is partly supported by the grant from the Chinese National Science and Technology Major Projects of New Drugs (2009ZX09301-004).

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Authors and Affiliations

  1. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China

    Guo-xing Zhong, Yi Gong, Chuan-jiang Yu, Shi-fei Wu, Qing-ping Ma, Yu Wang, Jiang Ren, Xue-chao Zhang, Wei-han Yang & Wen Zhu

  2. Central Laboratory, Shenzhen Baoan Maternal and Child Health Hospital, Shenzhen, 518133, China

    Guo-xing Zhong

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  1. Guo-xing Zhong
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  2. Yi Gong
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Correspondence to Wen Zhu.

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Zhong, Gx., Gong, Y., Yu, Cj. et al. Significantly inhibitory effects of low molecular weight heparin (Fraxiparine) on the motility of lung cancer cells and its related mechanism. Tumor Biol. 36, 4689–4697 (2015). https://doi.org/10.1007/s13277-015-3117-8

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