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Effect of cell cycle phase on the sensitivity of SAS cells to sonodynamic therapy using lowintensity ultrasound combined with 5aminolevulinic acid in vitro

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Sonodynamic therapy (SDT) with 5aminolevulinic acid (5ALA) can effectively inhibit various types of tumor in vitro and in vivo. However, the association between the efficacy of SDT and the phase of the cell cycle remains to be elucidated. 5ALA may generate different quantities of sonosensitizer, protoporphyrin IX (PpIX), in different phases of the cell cycle, which may result in differences in sensitivity to 5ALAinduced SDT. The present study aimed to investigate the effect of the cell cycle on the susceptibility of SAS cells to SDT following synchronization to different cell cycle phases. These results indicates that the rates of cell death and apoptosis of the SAS cells in the S and G2/M phases were significantly higher following SDT, compared with those in the G1phase cells and unsynchronized cells, with a corresponding increase in PpIX in the S and G2/M cells. In addition, the expression of caspase3 increased, while that of Bcell lymphoma (Bcl)2 decreased markedly in theS and G2/M cells following SDT. Cyclin A was also expressed at higher levels in the S and G2/M cells, compared with the G1phase cells. SDT also caused a significant upregulation of cyclin A in all phases of the cell cycle, however this was most marked in the S and G2/M cells. It was hypothesized that high expression levels of cyclin A in the S and G2/M cells may promote the induction of caspase3 and reduce the induction of Bcl2 by SDT and, therefore, enhance apoptosis. Taken together, these data demonstrated that cells in The S and G2/M phases generate more intracellular PpIX, have higher levels of cyclin A and are, therefore, more sensitive to SDTinduced cytotoxicity. These findings indicate the potential novel approach to preventing the onset of cancer by combining cellcycle regulators with SDT. This sequential combination therapy may be a simple and costeffective way of enhancing the effects of SDT in clinical settings.
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Document Type: Research Article

Affiliations: 1: Department of Oral Maxillofacial Surgery, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China 2: Department of Stomatology, the Fourth Clinical College, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China 3: Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China 4: Laboratory of Sono and Phototheranostic Technologies, Harbin Institute of Technology, Harbin, Heilongjiang 150080, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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