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

Research output: Contribution to journalArticle

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
Externally publishedYes

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Renal Cell Carcinoma
Liposomes
Genes
Apoptosis
Urinary Bladder Neoplasms
Prostatic Neoplasms
Proteins
Tetrazolium Salts
Cell Line
Severe Combined Immunodeficiency
Proximal Kidney Tubule
Acridine Orange
Human Activities
Genetic Therapy
Immunotherapy
Research Design
Therapeutics
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Staining and Labeling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nakanishi, H., Mizutani, Y., Kawauchi, A., Ukimura, O., Shiraishi, T., Hatano, M., ... 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.

Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-β gene against human renal cell carcinoma. / Nakanishi, Hiroyuki; Mizutani, Yoichi; Kawauchi, Akihiro; Ukimura, Osamu; Shiraishi, Takumi; Hatano, Manabu; Mizuno, Masaaki; Yoshida, Jun; Miki, Tsuneharu.

In: Clinical Cancer Research, Vol. 9, No. 3, 01.03.2003, p. 1129-1135.

Research output: Contribution to journalArticle

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, vol. 9, no. 3, pp. 1129-1135.
Nakanishi H, Mizutani Y, Kawauchi A, Ukimura O, Shiraishi T, Hatano M et al. Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-β gene against human renal cell carcinoma. Clinical Cancer Research. 2003 Mar 1;9(3):1129-1135.
Nakanishi, Hiroyuki ; Mizutani, Yoichi ; Kawauchi, Akihiro ; Ukimura, Osamu ; Shiraishi, Takumi ; Hatano, Manabu ; Mizuno, Masaaki ; Yoshida, Jun ; Miki, Tsuneharu. / Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-β gene against human renal cell carcinoma. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 3. pp. 1129-1135.
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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.",
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AU - Mizutani, Yoichi

AU - Kawauchi, Akihiro

AU - Ukimura, Osamu

AU - Shiraishi, Takumi

AU - Hatano, Manabu

AU - Mizuno, Masaaki

AU - Yoshida, Jun

AU - Miki, Tsuneharu

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N2 - 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.

AB - 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.

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