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Targeting interleukin-4 receptor alpha by hybrid Peptide for novel biliary tract cancer therapy.

Seto K, Shoda J, Horibe T, Warabi E, Kohno M, Yanagawa T, Bukawa H, Nakanuma Y, Kawakami K - Int J Hepatol (2014)

Bottom Line: It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors.We also showed that IL-4R α -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro.In addition, intravenous administration of IL-4R α -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan ; Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

ABSTRACT
It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R α -lytic hybrid peptide composed of binding peptide to IL-4R α and cell-lytic peptide and reported that the designed IL-4R α -lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4R α . Here, we evaluated the antitumor activity of the IL-4R α -lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R α -lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5  μ M. We also showed that IL-4R α -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4R α -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R α -lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.

No MeSH data available.


Related in: MedlinePlus

Cytotoxic activity of IL-4Rα-lytic hybrid peptide. Six BTC cell lines were cultured with various concentrations of IL-4Rα-lytic hybrid peptide or lytic peptide (0–20 μM) for 72 h, and cytotoxic activity was assessed using WST-8 reagent. The results are represented as mean ± SD (bars) of triplicate determinations, and the assay was repeated three times.
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fig2: Cytotoxic activity of IL-4Rα-lytic hybrid peptide. Six BTC cell lines were cultured with various concentrations of IL-4Rα-lytic hybrid peptide or lytic peptide (0–20 μM) for 72 h, and cytotoxic activity was assessed using WST-8 reagent. The results are represented as mean ± SD (bars) of triplicate determinations, and the assay was repeated three times.

Mentions: To assess the in vitro cytotoxic activity of IL-4Rα-lytic hybrid peptide to BTC cell lines, the WST assay was performed using BTC cell lines treated with IL-4Rα-lytic hybrid peptide and lytic peptide (Figure 2). TGBC-1-TKB, TGBC-44-TKB, CCKS-1, KKU-100, and KMBC were sensitive to IL-4Rα-lytic hybrid peptide; the concentration that killed 50% of all cells (IC50) was less than 3.5 μM. Sk-ChA-1 was also sensitive to IL-4Rα-lytic hybrid peptide with an IC50 of less than 4.5 μM. In contrast, optimal cell killing was not induced in these cells by lytic peptide. The cytotoxic activity of the hybrid peptide was strongly enhanced when compared with that of the lytic peptide. The cytotoxic activity of IL-4Rα-lytic hybrid peptide increased 3.0–7.8-fold stronger than that of lytic peptide in BTC cell lines (Table 1).


Targeting interleukin-4 receptor alpha by hybrid Peptide for novel biliary tract cancer therapy.

Seto K, Shoda J, Horibe T, Warabi E, Kohno M, Yanagawa T, Bukawa H, Nakanuma Y, Kawakami K - Int J Hepatol (2014)

Cytotoxic activity of IL-4Rα-lytic hybrid peptide. Six BTC cell lines were cultured with various concentrations of IL-4Rα-lytic hybrid peptide or lytic peptide (0–20 μM) for 72 h, and cytotoxic activity was assessed using WST-8 reagent. The results are represented as mean ± SD (bars) of triplicate determinations, and the assay was repeated three times.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020457&req=5

fig2: Cytotoxic activity of IL-4Rα-lytic hybrid peptide. Six BTC cell lines were cultured with various concentrations of IL-4Rα-lytic hybrid peptide or lytic peptide (0–20 μM) for 72 h, and cytotoxic activity was assessed using WST-8 reagent. The results are represented as mean ± SD (bars) of triplicate determinations, and the assay was repeated three times.
Mentions: To assess the in vitro cytotoxic activity of IL-4Rα-lytic hybrid peptide to BTC cell lines, the WST assay was performed using BTC cell lines treated with IL-4Rα-lytic hybrid peptide and lytic peptide (Figure 2). TGBC-1-TKB, TGBC-44-TKB, CCKS-1, KKU-100, and KMBC were sensitive to IL-4Rα-lytic hybrid peptide; the concentration that killed 50% of all cells (IC50) was less than 3.5 μM. Sk-ChA-1 was also sensitive to IL-4Rα-lytic hybrid peptide with an IC50 of less than 4.5 μM. In contrast, optimal cell killing was not induced in these cells by lytic peptide. The cytotoxic activity of the hybrid peptide was strongly enhanced when compared with that of the lytic peptide. The cytotoxic activity of IL-4Rα-lytic hybrid peptide increased 3.0–7.8-fold stronger than that of lytic peptide in BTC cell lines (Table 1).

Bottom Line: It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors.We also showed that IL-4R α -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro.In addition, intravenous administration of IL-4R α -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan ; Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

ABSTRACT
It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R α -lytic hybrid peptide composed of binding peptide to IL-4R α and cell-lytic peptide and reported that the designed IL-4R α -lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4R α . Here, we evaluated the antitumor activity of the IL-4R α -lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R α -lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5  μ M. We also showed that IL-4R α -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4R α -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R α -lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.

No MeSH data available.


Related in: MedlinePlus