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Expression of IL-13Rα2 in liver cancer cells and its effect on targeted therapy of liver cancer

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Abstract

Purpose

Liver cancer is the third leading cause of cancer-related deaths globally. The number of liver cancers diagnosed in the world is increasing at an alarming rate. It is of great significance to find the new targets of the tumor cells and specific medicine. This research investigated the expression of interleukin-13 receptor α2 (IL-13Rα2) in different liver cancer cell lines and liver cancer tissues, and assessed the cytotoxin DT389-hIL13-13E13K (IL-13 and diphtheria toxin fusion protein) targeted killing effect on liver cancer cells. Based on study above, we further analyzed the function of IL-13Rα2 on the targeted liver cancer therapy. The results will provide a novel strategy and an alternative way for liver cancer therapy.

Methods

The expression of IL-13Rα2 in different liver cancer cell lines and tissues were analyzed by RT-PCR and immunohistochemistry. Cytotoxicity assay of DT389-hIL13-13E13K was performed in eight different concentrations in liver cancer cell lines in vitro. At the same time, siRNA-mediated knockdown was introduced to assess the role of IL-13Rα2 in liver cancer therapy.

Results

Two out of four tested liver cancer cell lines and 27 out of 33 (81.82%) liver tissues expressed the IL-13Rα2. The fusion protein DT389-hIL13-13E13K showed a moderate cytotoxicity to the cancer cell line BEL-7402 in vitro, which 50% inhibition (IC50) concentration occurred at 1.4 × 10−5 M. Besides, the sensitivity to fusion protein DT389-hIL13-13E13K was decreased in siRNA-transfected liver cells compared with control ones. These results suggest that IL-13Rα2 chain is a specific target for IL-13-directed fusion protein.

Conclusions

We reported the expression of IL-13Rα2 in liver cancer cell lines and tissues as well as investigated the cytotoxin (DT389-hIL13-13E13K) targeted killing efficiency of liver cancer cells and potential role of IL-13Rα2 in the cancer treatment.

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Acknowledgments

This work was supported by the Great Science and Technology Foundation of Beijing Jiaotong University (Grand No. 2004SZ010), and National Infrastructure of Natural Science and Technology Program (2005DKA21101), and Key Projects in the National Science and Technology Pillar Program during the Eleventh Five-Year Plan Period (2008BAK41B01-5). The authors thank Dr. Fuchou Tang for critical reading of the manuscript.

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Correspondence to Lingling Hou, Weijun Guan or Yuehui Ma.

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Lingling Hou and Juan Du contributed equally to this work.

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Hou, L., Du, J., Wang, J. et al. Expression of IL-13Rα2 in liver cancer cells and its effect on targeted therapy of liver cancer. J Cancer Res Clin Oncol 136, 839–846 (2010). https://doi.org/10.1007/s00432-009-0724-z

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  • DOI: https://doi.org/10.1007/s00432-009-0724-z

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