Inhibition of melanoma by ultrasound-microbubble-aided drug delivery suggests membrane permeabilization

Shozo Sonoda, Katsuro Tachibana, Eisuke Uchino, Toshifumi Yamashita, Kenji Sakoda, Koh Hei Sonoda, Toshio Hisatomi, Yuichi Izumi, Taiji Sakamoto

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52 Citations (Scopus)


Ultrasound exposure-induced cavitation has been shown to accentuate cell membrane permeability, thus promoting effective drug delivery into cells, a technique that can be enhanced in the presence of microbubbles (MB). Here we applied this method as a treatment for malignant melanoma of the eyelid. The incidence of malignant melanoma in ophthalmology is relatively high, but its treatment is cosmetically difficult. A greater in vitro growth suppression of B-16 melanoma cells was achieved using ultrasound and MB in combination with the anticancer drug bleomycin than when a more concentrated dose of bleomycin alone was applied to the cell culture. Moreover, this effect was enhanced in an in vivo tumor model created by injecting B-16 melanoma cells into the lower eyelids of SCID mice. The antitumor effect of bleomycin was observed at a lower dose (0.5 mg/ml) when the treatment was used in conjunction with ultrasound. The effect was further enhanced when MB were included, with tumor shrinkage occurring at bleomycin levels of 0.06 mg/ml. These results show that ultrasound and MB promote efficient bleomycin uptake by cells, and that the technique is a potentially useful drug delivery method.

Original languageEnglish
Pages (from-to)1282-1289
Number of pages8
JournalCancer Biology and Therapy
Issue number8
Publication statusPublished - Aug 2007

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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