Significant antitumor activity of cationic multilamellar liposomes containing human interferon-β gene in combination with 5-fluorouracil against human renal cell carcinoma

  • Authors:
    • Kosuke Yamamoto
    • Yoichi Mizutani
    • Hiroyuki Nakanishi
    • Jun Fujiwara
    • Hirokazu Ishida
    • Daisuke Toiyama
    • Koichi Abe
    • Issei Hayashi
    • Koichi Okada
    • Akihiro Kawauchi
    • Masaaki Mizuno
    • Jun Yoshida
    • Tsuneharu Miki
  • View Affiliations

  • Published online on: September 1, 2008     https://doi.org/10.3892/ijo_00000041
  • Pages: 565-571
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Abstract

Immunotherapy is one of the most effective treatments against metastatic renal cell carcinoma (RCC). However, the response rate is not high. Therefore, more effective therapies are necessary for patients with metastatic RCC. We previously reported on the significant antitumor activity of cationic multilamellar liposome containing human interferon-β (huIFN-β) gene (IAB-1) against RCC. We then examined the antitumor effect of IAB-1 in combination with anticancer drugs against RCC. The cytotoxicity of IAB-1 alone, and in combination with anticancer drugs, cisplatin, adriamycin, 5-fluorouracil, gemcitabine, paclitaxel and irinotecan hydrochloride against the human RCC cell line NC65 was examined by the colorimetric method using tetrazolium salt. For the in vivo study, we used NC65 cells inoculated into the severe combined immunodeficiency mouse. The results showed that the in vitro combination therapy with IAB-1 and 5-FU was more cytotoxic than IAB-1 alone. However, synergistic cytotoxicity was not observed when combined with IAB-1 and other anticancer drugs. NC65 tumors transfected with IAB-1 in mice were smaller than those receiving an injection of empty liposome or the recombinant huIFN-β protein. Treatment with IAB-1 in combination with 5-FU resulted in significant anticancer activity. IAB-1 enhanced the activity of thymidine phosphorylase (TP), which converts 5-FU to the active metabolite, FdUMP. In contrast, IAB-1 decreased the activity of thymidylate synthase (TS), which is a target enzyme of 5-FU. In conclusion, these findings indicate that a combination of IAB-1 and 5-FU may have enhanced antitumor activity against human RCC, suggesting its potential clinical application. The mechanism of enhanced cytotoxicity by combination therapy with IAB-1 and 5-FU may up-regulate TP activity and down-regulate TS activity.

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September 2008
Volume 33 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yamamoto K, Mizutani Y, Nakanishi H, Fujiwara J, Ishida H, Toiyama D, Abe K, Hayashi I, Okada K, Kawauchi A, Kawauchi A, et al: Significant antitumor activity of cationic multilamellar liposomes containing human interferon-β gene in combination with 5-fluorouracil against human renal cell carcinoma. Int J Oncol 33: 565-571, 2008.
APA
Yamamoto, K., Mizutani, Y., Nakanishi, H., Fujiwara, J., Ishida, H., Toiyama, D. ... Miki, T. (2008). Significant antitumor activity of cationic multilamellar liposomes containing human interferon-β gene in combination with 5-fluorouracil against human renal cell carcinoma. International Journal of Oncology, 33, 565-571. https://doi.org/10.3892/ijo_00000041
MLA
Yamamoto, K., Mizutani, Y., Nakanishi, H., Fujiwara, J., Ishida, H., Toiyama, D., Abe, K., Hayashi, I., Okada, K., Kawauchi, A., Mizuno, M., Yoshida, J., Miki, T."Significant antitumor activity of cationic multilamellar liposomes containing human interferon-β gene in combination with 5-fluorouracil against human renal cell carcinoma". International Journal of Oncology 33.3 (2008): 565-571.
Chicago
Yamamoto, K., Mizutani, Y., Nakanishi, H., Fujiwara, J., Ishida, H., Toiyama, D., Abe, K., Hayashi, I., Okada, K., Kawauchi, A., Mizuno, M., Yoshida, J., Miki, T."Significant antitumor activity of cationic multilamellar liposomes containing human interferon-β gene in combination with 5-fluorouracil against human renal cell carcinoma". International Journal of Oncology 33, no. 3 (2008): 565-571. https://doi.org/10.3892/ijo_00000041