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Regulation of chemosensitivity and migration by clusterin in non-small cell lung cancer cells

Cancer Chemotherapy and Pharmacology volume 69, pages 145–154 (2012)Cite this article

Abstract

Purpose

In terms of drug resistance, cancer cells usually benefit from high clusterin (CLU) expression on chemotherapy. In contrast, CLU expression has been found to be a favorable prognostic factor in lung cancer patients. The aims of this study are to determine the association between CLU expression and chemotherapeutic sensitivity and the potential role of CLU in migration in human non-small-cell lung cancer (NSCLC) cell lines.

Methods

The levels of clusterin in NSCLC cell lines were altered by short hairpin RNA interference (shRNAi) and overexpression on chemosensitivity assay. Migratory ability of these cell lines was also investigated.

Results

H1355 cells with the highest level of CLU demonstrated the lowest sensitivities to Adriamycin (ADR), docetaxel (DOC), and gemcitabine (GEM) treatment. Inhibition of CLU expression in H1355 cells resulted in higher chemosensitivities. When CLU was stably overexpressed in A549 and H1299 cells, only the chemosensitivity to ADR was reduced. The migratory ability of CLU-overexpressing cells significantly decreased. Moreover, MMP2 transcription was inhibited in CLU-overexpressing H1299 cells. These results indicated lower metastatic potential for cancer cells with high CLU level.

Conclusion

Lung cancer cells with high level of CLU have reduced chemosensitivity. High level of CLU may result in migratory inhibition and thus favorable prognosis in lung cancer.

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Acknowledgments

This work was supported by grants (NSC-96-2314-B-040-017-MY3 and 98-CCH-CSMU-02) to G-T Sheu. We would also like to thank the staff of the Instrument Center of Chung Shan Medical University for their technical support. This center is partly supported by the National Science Council, Ministry of Education and Chung Shan Medical University.

Conflict of interest

The authors declare that there are no potential conflicts of interest.

Author information

Affiliations

  1. Division of General Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, 135 Nanxiao St., Changhua City, Changhua County, 500, Taiwan

    Ching-Yuan Cheng

  2. Department of Biotechnology, Hung Kuang University, 34 Chung-Chie Rd, Sha Lu, Taichung City, 443, Taiwan

    Shur-Hueih Cherng

  3. Institute of Medicine, Chung Shan Medical University, Research Building Room 702, No. 110, Sec. 1, Jianguo N. Road, Taichung City, 402, Taiwan

    Wen-Jun Wu, Tsung-Ying Yang, Xin-Yi Huang, Fu-Tien Liao & Gwo-Tarng Sheu

  4. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 160, Sec. 3, Chung-Kang Rd., Taichung City, 407, Taiwan

    Tsung-Ying Yang

  5. Department of Medical Oncology, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung City, 402, Taiwan

    Ming-Fang Wu

Authors
  1. Ching-Yuan Cheng
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  2. Shur-Hueih Cherng
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  3. Wen-Jun Wu
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  5. Xin-Yi Huang
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  6. Fu-Tien Liao
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  7. Ming-Fang Wu
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  8. Gwo-Tarng Sheu
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Correspondence to Gwo-Tarng Sheu.

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Cheng, CY., Cherng, SH., Wu, WJ. et al. Regulation of chemosensitivity and migration by clusterin in non-small cell lung cancer cells. Cancer Chemother Pharmacol 69, 145–154 (2012). https://doi.org/10.1007/s00280-011-1682-0

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  • DOI: https://doi.org/10.1007/s00280-011-1682-0

Keywords

  • Lung cancer
  • Clusterin
  • Chemosensitivity
  • Migration