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Exosome-mediated transfer of CLIC1 contributes to the vincristine-resistance in gastric cancer

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Abstract

Our previous study shows that high Chloride intracellular channel 1 (CLIC1) expression can efficiently enhance invasion and migration of gastric cancer (GC) cells in vitro. Growing evidences have found that exosomes are involved in chemotherapy resistance in several cancers including GC. We aimed to evaluate the effect of the exosome-mediated transfer of CLIC1 in the vincristine-resistance of GC. The effect of exosome-mediated transfer of CLIC1 on the development of resistance to vincristine in GC cell line SGC-7901 and the potential underlying mechanisms were investigated by Cell Counting Kit-8 (CCK8), RT-PCR, and Western blotting. Exosomes were isolated from cell supernatants by differential ultracentrifugation. Comparing with SGC-7901, the expression level of CLIC1 is higher in vincristine‑resistant cell line SGC-7901/VCR (P < 0.05). After silencing the expression of CLIC1 by RNA interference, the half inhibition concentration (IC50) to vincristine decreased significantly in SGC-7901/VCR, and the expression of CLIC1 decreased significantly in exosomes from SGC-7901/VCR. After 48 h co-culturing with exosomes from SGC-7901/VCR, the IC50 to vincristine in SGC-7901 increased significantly, and the expression of CLIC1, P-gp, and Bcl-2 were significantly up-regulated. CLIC1 was closely associated with the resistance to vincristine in GC, and exosome-mediated transfer of CLIC1 could induce the development of resistance to vincristine in vitro. The possible mechanism was related to up-regulated P-gp and Bcl-2. However, in vivo study was needed to confirm the results in future.

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Funding

This manuscript was supported by Natural Science Foundation of Guangxi (2018GXNSFBA281159), Youth Foundation of Guangxi Medical University (GXMUYSF201506), and Youth Teacher Foundation of Guangxi Education Department (2017KY0110).

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  1. Kun Zhao and Zhen Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China

    Kun Zhao, Zhen Wang, Xin Li, Jin-lu Liu, Lei Tian & Jun-qiang Chen

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  1. Kun Zhao
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  2. Zhen Wang
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  3. Xin Li
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  4. Jin-lu Liu
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  5. Lei Tian
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  6. Jun-qiang Chen
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Correspondence to Lei Tian or Jun-qiang Chen.

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Zhao, K., Wang, Z., Li, X. et al. Exosome-mediated transfer of CLIC1 contributes to the vincristine-resistance in gastric cancer. Mol Cell Biochem 462, 97–105 (2019). https://doi.org/10.1007/s11010-019-03613-9

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  • DOI: https://doi.org/10.1007/s11010-019-03613-9

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