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The effect of S1P receptor signaling pathway on the survival and drug resistance in multiple myeloma cells

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Abstract

Multiple myeloma (MM) remains incurable by conventional chemotherapy. Sphingosine-1-phosphate (S1P) receptor-mediated signaling has been recently demonstrated to have critical roles in cell survival and drug resistance in a number of hematological malignancies. To dissect the roles of S1P receptor pathway in MM, we systematically examined cell viability and protein expression associated with cell survival and drug resistance in MM cell lines upon treatment with either pathway activator (S1P) or inhibitor (FTY720). Our results reveal that FTY720 inhibits cell proliferation by downregulating expression of target genes, while S1P has an opposite effect. Knocking down of S1P receptor S1P5R results in a reduction of cell survival-related gene expression; however, it does not have impacts on expression of drug resistance genes. These results suggest that S1P signaling plays a role in cell proliferation and drug resistance in MM, and targeting this pathway will provide a new therapeutic direction for MM management.

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Funding

This work was supported by the Natural Science Foundation of China (81272629).

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    Authors and Affiliations

    1. Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China

      Di Fu, Yingchun Li, Jia Li, Xiaoyan Shi, Ronghui Yang, Yuan Zhong, Huihan Wang & Aijun Liao

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    1. Di Fu
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    2. Yingchun Li
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    3. Jia Li
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    4. Xiaoyan Shi
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    8. Aijun Liao
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    Correspondence to Aijun Liao.

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    Di Fu and Yingchun Li contributed equally to this work.

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    Fu, D., Li, Y., Li, J. et al. The effect of S1P receptor signaling pathway on the survival and drug resistance in multiple myeloma cells. Mol Cell Biochem 424, 185–193 (2017). https://doi.org/10.1007/s11010-016-2854-3

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