Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin

•Efficacy of sonodynamic therapy (SDT) with bleomycin was studied in EMT-6 cells.•SDT with bleomycin was more cytotoxic than SDT alone.•In vivo, SDT with bleomycin achieved greater tumor growth inhibition than SDT alone.•Bleomycin improved the efficacy of SDT.•SDT with bleomycin might be a noninvasi...

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Veröffentlicht in:Ultrasonics 2016-04, Vol.67, p.76-84
Hauptverfasser: Osaki, Tomohiro, Ono, Misato, Uto, Yoshihiro, Ishizuka, Masahiro, Tanaka, Tohru, Yamanaka, Nobuyasu, Kurahashi, Tsukasa, Azuma, Kazuo, Murahata, Yusuke, Tsuka, Takeshi, Ito, Norihiko, Imagawa, Tomohiro, Okamoto, Yoshiharu
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Sprache:eng
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Zusammenfassung:•Efficacy of sonodynamic therapy (SDT) with bleomycin was studied in EMT-6 cells.•SDT with bleomycin was more cytotoxic than SDT alone.•In vivo, SDT with bleomycin achieved greater tumor growth inhibition than SDT alone.•Bleomycin improved the efficacy of SDT.•SDT with bleomycin might be a noninvasive treatment for deep-seated tumors. Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound and a sonosensitizer agent. We examined whether 5-aminolevulinic acid (5-ALA)-based SDT at 1 or 3MHz could enhance the cytotoxicity of bleomycin (BLM) toward mouse mammary tumor cells both in vitro and in vivo. At 1MHz, cell viability in the 5-ALA-based SDT group at 1, 2, and 3W/cm2 was 34.30%, 50.90%, and 60.16%, respectively. Cell viability in the 5-ALA-based SDT+BLM group at 1, 2, and 3W/cm2 was 0.09%, 0.32%, and 0.17%, respectively. In contrast, at 3MHz, 5-ALA-based SDT+BLM did not show pronounced cytotoxicity. In the in vivo study, 5-ALA-based SDT+BLM was significantly more cytotoxic than 5-ALA-based SDT at 1MHz and 3MHz. These findings suggest that the mechanism of tumor shrinkage induced by 5-ALA-based SDT+BLM might involve not only direct cell killing, but also vascular shutdown. Thus, we show here that 5-ALA-based SDT enhances the efficacy of BLM both in vitro and in vivo.
ISSN:0041-624X
1874-9968
DOI:10.1016/j.ultras.2016.01.003