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Synergistic antitumor effect of CXCL10 with hyperthermia

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Abstract

Purpose

IFN–inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) has been described as an antiangiogenic chemokine and displays a potent antitumor activity in vivo. In the present study, we try to investigate whether the combination therapy of hyperthermia, a physical antiangiogenic modality, with CXCL10 would completely eradicate the established solid tumors.

Methods

Immunocompetent BALB/c mice bearing Meth A fibrosarcoma were established. Mice were treated with either CXCL10 at 25 μg/kg once a day for 20 days, hyperthermia was given twice (at 42°C for 1 h, on day 6 and 12 after the initiation of CXCL10), or together. Tumor volume and survival time were observed. The microvessel density was determined by CD31 immunofluorescence. Histologic analysis and assessment of apoptotic cells were also conducted in tumor tissues.

Results

The results showed that CXCL10 and hyperthermia inhibited the growth of Meth A fibrosarcoma and interestingly, the combination therapy enhanced the antiangiogenic effects and completely eradicated the established solid tumors. Histological examination revealed that CXCL10 + hyperthermia led to increased induction of apoptosis, tumor necrosis, and elevated lymphocyte infiltration compared with the controls. Moreover, the tumor eradicated animals developed a protective T-cell-dependent antitumor memory response against Meth A tumor cells rechallenge.

Conclusions

Our finding is that the combination therapy can achieve a synergistic antitumor efficacy, supporting the idea that the combination of two antiangiogenic agents may lead to improved clinical outcome. These findings could open new perspectives in clinical antitumor therapy.

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Acknowledgments

This work was supported by National Basic Research Program of China (2001CB510001, 2004CB518800), the projects of National Natural Science Foundation of China, and National 863 Program.

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Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 1# Keyuan Road 4, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, People’s Republic of China

    Ping Chen, Ling-lin Yang, Han-shuo Yang, Yong-sheng Wang, Gang Li, Yang Wu, Fang Fang, Kang Liu, Jie Li, Xia Zhao, Huo-zhen Hu & Yu-quan Wei

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  1. Ping Chen
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  2. Ling-lin Yang
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  3. Han-shuo Yang
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  5. Gang Li
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  7. Fang Fang
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  10. Xia Zhao
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  11. Huo-zhen Hu
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Corresponding authors

Correspondence to Huo-zhen Hu or Yu-quan Wei.

Additional information

Ping Chen, Ling-lin Yang, Huo-zhen Hu, and Yu-quan Wei contributed equally to this work.

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Chen, P., Yang, Ll., Yang, Hs. et al. Synergistic antitumor effect of CXCL10 with hyperthermia. J Cancer Res Clin Oncol 134, 679–687 (2008). https://doi.org/10.1007/s00432-007-0337-3

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  • DOI: https://doi.org/10.1007/s00432-007-0337-3

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