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Sphingosine Kinase-1 Activation Causes Acquired Resistance Against Sunitinib in Renal Cell Carcinoma Cells

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Abstract

Multi-target tyrosine kinase inhibitor Sunitinib has been widely used in cancer treatment, including metastatic renal cell carcinoma. However, most patients who initially benefit from Sunitinib develop resistance with extended usage of Sunitinib, which is referred to as “acquired resistance”. The molecular mechanisms contributing to this acquired resistance remain poorly understood. In this present study, we established Sunitinib-resistant cell lines from human renal cell lines (786-O, A498, ACHN and CAKI1) by continuous treatment with Sunitinib to explore the molecular mechanism leading to Sunitinib resistance. We found that PDGFR-β expression in cell seems to be a protective factor against Sunitinib resistance formation. In addition, we found that both SK1 and ERK were activated in Sunitinib-resistance cell lines and SK1 and ERK inhibitors could resensitize Sunitinib-resistant cell lines. In conclusion, our observations suggest that SK1 and ERK activation is a feature of resistant cell lines, which serves as an alternative pathway evading anti-tumor activity of Sunitinib.

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Acknowledgments

This work was supported by the Funds of Chongqing Normal University (No. 12XLB025).

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Authors and Affiliations

  1. Medical College, Qingdao University, Qingdao, 266023, Shandong, China

    Hui Gao

  2. Department of Oncology, The Affiliated Jiangyin People’s Hospital, School of Medicine, Southeast University, Jiangyin, 214400, China

    Lichun Deng

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  1. Hui Gao
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  2. Lichun Deng
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Correspondence to Lichun Deng.

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Gao, H., Deng, L. Sphingosine Kinase-1 Activation Causes Acquired Resistance Against Sunitinib in Renal Cell Carcinoma Cells. Cell Biochem Biophys 68, 419–425 (2014). https://doi.org/10.1007/s12013-013-9723-4

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  • DOI: https://doi.org/10.1007/s12013-013-9723-4

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