[Combination therapy of high energy under water shock waves and anticancer drugs for subcutaneous murine bladder cancer (MBT-2)]

Abstract

The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively.