Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-β gene against human renal cell carcinoma

Hiroyuki Nakanishi, Yoichi Mizutani, Akihiro Kawauchi, Osamu Ukimura, Takumi Shiraishi, Manabu Hatano, Masaaki Mizuno, Jun Yoshida, Tsuneharu Miki

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Abstract

Purpose: Immunotherapy is the most effective treatment against metastatic renal cell carcinoma (RCC). However, the response rate is ∼15%. More effective therapy is, therefore, needed for patients with metastatic RCC. We then examined the antitumor effect of cationic multilamellar liposome containing human IFN-β (huIFN-β) gene (IAB-1) against RCC. Experimental Design: Concentrations of huIFN-β protein were measured by ELISA. The cytotoxicity of IAB-1 against human RCC (NC65, ACHN, and freshly isolated RCC cells), prostate and bladder cancer cell lines, and renal proximal tubule endothelial cells (RPTEC5899) was examined by the colorimetric method using tetrazolium salt. Apoptosis was assessed by the acridine-orange staining. For in vivo study, we used NC65 cells inoculated into severe combined immunodeficiency mouse. Results: The RCC cells treated with IAB-1 secreted significant amounts of huIFN-β protein continuously. Drastic in vitro cytotoxic effect of IAB-1 against RCC was observed. In contrast, treatment with 1000 IU/ml recombinant huIFN-β protein resulted in weak cytotoxicity. The cytotoxic effect against prostate and bladder cancer cell lines was less than that against RCC. Furthermore, no significant cytotoxicity was observed in RPTEC5899 cells. Apoptosis was observed in the cells treated with IAB-1, but recombinant huIFN-β failed to induce apoptosis. The size of NC65 tumors transfected with IAB-1 in mice was significantly smaller than that receiving injection of empty liposome or recombinant huIFN-β protein. Conclusion: These findings indicate that IAB-1 may have an antitumor activity against human RCC by inducing apoptosis, suggesting its potential clinical application for gene therapy against RCC.

Original languageEnglish (US)
Pages (from-to)1129-1135
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number3
StatePublished - Mar 1 2003

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nakanishi, H., Mizutani, Y., Kawauchi, A., Ukimura, O., Shiraishi, T., Hatano, M., Mizuno, M., Yoshida, J., & Miki, T. (2003). Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-β gene against human renal cell carcinoma. Clinical Cancer Research, 9(3), 1129-1135.