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Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma

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Tumor Biology

Abstract

Eg5 is critical for mitosis and overexpressed in various malignant tumors, which has now been identified as a promising target in cancer therapy. However, the anti-cancer activity of Eg5 inhibitor in renal cell carcinoma (RCC) remains an open issue. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking Eg5 by S-(methoxytrityl)-l-cysteine (S(MeO)TLC) in RCC both in vitro and vivo. The expression of Eg5 was examined in clinical tissue samples and various kidney cell lines, including 293T, 786-0, and OS-RC-2. The anti-proliferative activity of Eg5 inhibitors, (S)-trityl-l-cysteine (STLC) and S(MeO)TLC, was evaluated by a cell viability assay. An apoptosis assay with Hoechst nuclear staining and flow cytometry was applied to investigate the efficacy of the S(MeO)TLC, which is more potent than STLC. Immunofluorescence was used to research the possible mechanism. Furthermore, in vivo studies were performed by using subcutaneous xenograft models, which were used to confirm its role as a potential anti-neoplastic drug. The Eg5 expression was detected in kidney cell lines and RCC tissues, which was low in normal kidney samples. STLC and S(MeO)TLC exhibited their optimal anti-proliferative activity in 72 h, and cells treated with S(MeO)TLC presented characteristic monoastral spindle phenotype in 24 h and apoptotic cells in 48 h. In vivo, S(MeO)TLC effectively suppressed tumor growth in subcutaneous xenograft models. Inhibition of Eg5 represses the proliferation of RCC in vitro and in vivo. All these findings collectively demonstrate that S(MeO)TLC, a potent Eg5 inhibitor, is a promising anti-cancer agent for the treatment of RCC.

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Acknowledgments

This study was supported by the grants from the National Natural Science Foundation of China (No. 81202017) and the Natural Science Foundation of Shandong Province (No. ZR2011HQ027).

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Ethics statement

All procedures were consistent with the National Institutes of Health Guide and approved by the institutional board with patients’ written consent. This study was evaluated and approved by the Ethics Committee of Provincial Hospital Affiliated to Shandong University.

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Authors and Affiliations

  1. Department of Urology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, Shandong, China

    Sentai Ding, Zuohui Zhao, Dingqi Sun, Fei Wu, Dongbin Bi, Jiaju Lu, Liang Sun, Haihu Wu & Kejia Ding

  2. Department of Urology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China

    Naidong Xing

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  1. Sentai Ding
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Correspondence to Sentai Ding.

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Sentai Ding and Zuohui Zhao contributed equally to this work.

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Ding, S., Zhao, Z., Sun, D. et al. Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma. Tumor Biol. 35, 7659–7668 (2014). https://doi.org/10.1007/s13277-014-2022-x

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