Sonochemotherapy of breast adenocarcinoma: an experimental in vivo model

Because the cytotoxic potential of hydrophilic drugs like bleomycin (BLM) is restricted by its low membrane permeability, the application of low-intensity ultrasound (US) on growing tumor cells enhances intracellular delivery of BLM after intratumoral administration, thereby potentiating its cytotoxicity. In the present study, the in vivo cell membrane permeability enhancement with US (1 MHz, 2, 5, and 10 min, ISPTA = 2 W/cm(2)) is compared with the murine model of breast adenocarcinoma in BALB/c mice.

Tumor induction was performed through a homograft surgery procedure. Mice were anesthetized before putting them in sonication situations. Sonications were done in an aquarium. Seven groups of the tumor-bearing mice, each consisting of eight mice, were sonicated without or after intratumoral injection of 0.1 ml BLM at different exposure times. The tumor volume was evaluated to assess the growth process by use of a digital caliper.

The results show that the BLM control group has a significant difference with BLM plus 10 min US on day 2 (p < 0.05). There is a significant difference between 2- and 10-min sonication on days 8 and 10 also. The difference between the Only US group and the other groups except Sham US was significant too (p < 0.05). Significant differences were seen only between the BLM plus US groups with Sham US and Only US control groups.

It has been concluded that for significant permeabilization of the cell membrane, sonication time for more than 10 min is required. Significant difference between the Only US and other groups indicates that US has a promoting effect on cell division procedure, in spite of the no-carcinogen effect of the US.