Abstract

To reveal the effect of tumor cell lines derived from different tissue on sonoporation efficiency under ultrasound microbubble (USMB) treatment, and meanwhile to determine the optimum parameter combination for each tumor cell line. Human breast tumor (MCF-7), ovarian tumor (A2780), liver tumor (Bel7402) and thyroid tumor (ARO) were exposed to ultrasound in the presence of SonoVue MBs. The major parameters for the designed experiments including MB concentration (A1:10%, A2:20%, A3:30%), sound intensity (B1:0.5, B2:1.0, B3:1.5W/cm2), irradiation time (C1:30, C2:60, C3:90s). An orthogonal array experimental design based on three levels L9 (33) of the above three parameters was employed to optimize the sonoporation efficiency. MTT experiment was used to calculate cell survival rate. FD500 uptake assay and cytometry were performed to evaluate transference percentage. The optimum parameter combination for each tumor cell line was different (MCF-7: A3B1C1, A2780: A1B3C3, Bel7402: A2B3C2, ARO: A2B3C2). Under their own optimum parameter combination, four kinds of tumor cell line exhibited different optimum sonoporation efficiency (MCF-7: 55.05±5.29%; A2780: 45.62±7.35%; Bel7402: 39.37±4.11%; ARO: 53.37±3.94%). Multiple comparison with LSD-t test showed that the sonoporation efficiency between four kinds of cell line was statistically significant (P<0.05), with the exception of MCF-7 VS. ARO (P=0.487). Tumor cell lines derived from different tissue can impact the sonoporation efficiency, and optimizing the exposure parameters can safely and efficiently increase the cell membrane permeability.

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