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hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes cervical cancer cells to a low dose of cisplatin

Cancer Gene Therapy volume 11, pages 1–7 (2004)Cite this article

Abstract

Cervical cancers at advanced stages or with recurrent status are mainly treated by platinum-based chemotherapy, such as cisplatin. However, a novel strategy to reduce the minimally effective dose is required to prevent severe adverse effects that limit the effectiveness of the treatment. Monocyte chemoattractant protein-1 (MCP-1) is a subtype of chemokines that can promote monocyte/macrophage infiltration and enhance their phagocytosis at not only sites of inflammatory lesions but also of tumors. The present study applies MCP-1-based gene therapy to treat cervical cancers. To achieve tumor-specific expression of MCP-1, retroviral expression vector was constructed using the human telomerase reverse transcriptase gene (hTERT) promoter. Retroviral expression of MCP-1 into cervical cancer ME180 cells did not affect their proliferation either in vitro or in vivo. However, when combined with a suboptimal low dose of cisplatin, tumor formation was obviously reduced in clones transduced with MCP-1, but not in control clones. Histological examination revealed that a substantial number of macrophages infiltrated the tumor sites of MCP-1-transduced cells, but not of controls. These findings suggest that MCP-1 expression sensitizes cervical cancer cells to an otherwise ineffective low dose of cisplatin, possibly by inducing the migration of macrophages to eradicate tumor cells. This system may be a novel strategy for chemotherapy combined with immunogene therapy against otherwise intractable cervical cancers.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, 13-1, Takaramachi, Kanazawa, 920-8641, Ishikawa, Japan

    Mitsuhiro Nakamura, Satoru Kyo, Taro Kanaya, Noriyuki Yatabe, Yoshiko Maida, Masaaki Tanaka & Masaki Inoue

  2. Division of Environmental Science, Forensic and Social Environmental Medicine, Graduate School of Medical Science, Kanazawa University, 13-1, Takaramachi, Kanazawa, 920-8641, Ishikawa, Japan

    Yuko Ishida & Toshikazu Kondo

  3. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University13-1, Takaramachi, Kanazawa, 920-8641, Ishikawa, Japan

    Mitsuhiro Nakamura, Chifumi Fujii & Naofumi Mukaida

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  1. Mitsuhiro Nakamura
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  2. Satoru Kyo
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Correspondence to Satoru Kyo.

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Nakamura, M., Kyo, S., Kanaya, T. et al. hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes cervical cancer cells to a low dose of cisplatin. Cancer Gene Ther 11, 1–7 (2004). https://doi.org/10.1038/sj.cgt.7700650

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  • DOI: https://doi.org/10.1038/sj.cgt.7700650

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