Effect of 5-fluorouracil, optison and ultrasound on MCF-7 cell viability

The aim of this study was to analyze cell viability and expression of apoptotic-related signaling proteins in MCF-7 breast cancer cells induced by combinations of ultrasound, the anticancer drug 5-fluorouracil (5-FU) and the ultrasound contrast agent Optison. MCF-7 cells were treated with 5-FU and sonicated at the frequency of 3.0 MHz and intensity of 3.0 W/cm² for 1 min in the presence of Optison. The cells were analyzed for lactate dehydrogenase (LDH) release (a measure of cytotoxicity) and cell proliferation (by MTT assays). The LDH/MTT ratio was used for assessment of cell death. Expression of the apoptotic-related proteins, Bax and p27^kip1, as well as phosphorylated forms of ERK and Akt proteins was assessed by Western blot analysis. We demonstrate that, immediately after treatment, cell death was most dependent on Optison; however, 24 h after treatment, cell death was more dependent on 5-FU. Ultrasound duty cycle increased cell death associated with either Optison or 5-FU. Furthermore, we show that treatment with 5-FU and ultrasound increased the levels of the Bax and p27^kip1proteins, but the addition of Optison appears to suppress apoptotic protein expression. (E-mail: [email protected]).