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Oxygen carrier YQ23 can enhance the chemotherapeutic drug responses of chemoresistant esophageal tumor xenografts

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Abstract

Purpose

Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia.

Methods

We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities.

Results

Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1α. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment.

Conclusions

In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients.

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Acknowledgments

This study was financially supported by research and development service agreement with New B Innovation Limited, Hong Kong.

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Authors and Affiliations

  1. Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

    Nikki P. Lee, Kin Tak Chan, Mei Yuk Choi, Ho Yu Lam, Lai Nar Tung, Daniel K. Tong & Simon Law

  2. New B Innovation Limited, Kowloon, Hong Kong

    Fei Chuen Tzang, Heron Han, Ian P. Y. Lam, Sui Yi Kwok, Sze Hang Lau, Cornelia Man & Bing L. Wong

  3. Queen Mary Hospital, Pokfulam, Hong Kong

    Daniel K. Tong & Simon Law

Authors
  1. Nikki P. Lee
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  2. Kin Tak Chan
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  3. Mei Yuk Choi
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  4. Ho Yu Lam
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  6. Fei Chuen Tzang
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  7. Heron Han
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  8. Ian P. Y. Lam
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  9. Sui Yi Kwok
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  11. Cornelia Man
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  12. Daniel K. Tong
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  13. Bing L. Wong
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  14. Simon Law
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Corresponding authors

Correspondence to Nikki P. Lee or Simon Law.

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Conflict of interest

Co-authors Fei Chuen Tzang, Heron Han, Ian P. Y. Lam, Sui Yi Kwok, Sze Hang Lau, Cornelia Man, and Bing L. Wong were under the employment of New B Innovation Limited when this study was performed. Other authors did not have any conflict of interest to declare.

Electronic supplementary material

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280_2015_2897_MOESM1_ESM.tif

Supplementary Figure 1: YQ23 demonstrates no obvious chemosensitizing effect towards cisplatin in cisplatin-sensitive HKESC-2 xenografts Treatment of cisplatin-sensitive HKESC-2 xenografts with cisplatin led to an obvious reduction in tumor size. However, such tumor reducing effect mediated by cisplatin (cisplatin) remained the same even after combined treatment with YQ23 (YQ23/cisplatin). This demonstrates YQ23 did not associate with any extra tumor-reducing effect on chemo-sensitive HKESC-2 xenografts (TIFF 793 kb).

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Lee, N.P., Chan, K.T., Choi, M.Y. et al. Oxygen carrier YQ23 can enhance the chemotherapeutic drug responses of chemoresistant esophageal tumor xenografts. Cancer Chemother Pharmacol 76, 1199–1207 (2015). https://doi.org/10.1007/s00280-015-2897-2

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  • DOI: https://doi.org/10.1007/s00280-015-2897-2

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