Enhancement of antitumor effects of 5-fluorouracil combined with ultrasound on Ehrlich ascites tumor in vivo

To evaluate the role of ultrasonic waves in enhancing the effect of 5-fluorouracil (5-FU) as anticancer drug, tumor growth, cell ultrastructure and temperature rises of ascites Ehrlich tumor implanted in mice were investigated at a frequency of 0.8 MHz. Different conditions of ultrasonic intensity (1, 2 and 3 W/cm), sonocation time (1, 3 and 5 min) and waveform (continuous and pulsed) were studied. A total of 10 mg/kg body weight of 5-FU was IV injected into the mice bearing Ehrlich tumors on days of 1, 3, 5, 8, 10 and 12 of therapy. After 24 h of each injection with 5-FU, tumor sites were sonocated at room temperature of 22degreesC. Tumor volumes were monitored by using ultrasonic imaging system during treatment just before each 5-FU injection, and on the 15th day of treatment. Density and ultrasonic attenuation of excised tumor tissues were measured in vitro and used to estimate the temperature rises due to ultrasonic absorption. Density and attenuation coefficients of excised tumor tissues were found to be dependent on the treatment regimen. The estimated rate of temperature rise and equilibrium temperature, and the characteristic time to reach equilibrium are given for each group. Results obtained indicate that tumor growth decreases with increasing of ultrasonic intensity and sonocation time. Tumor growth was delayed 4 to 6 days by combined treatment of 5- fluorouracil and ultrasound (US). Ultrastructure investigations of tumor cells showed severe damage in cytoplasmic organelles and cytoplasmic vacuoles that increased with increasing ultrasonic intensity and sonocation time. This damage appears as prominent crowded vacuoles among swollen ruptured organelles, chromatin fragments and severe increase in numbers of pyknotic and apoptotic cells.