Sinoporphyrin sodium based sonodynamic therapy induces anti-tumor effects in hepatocellular carcinoma and activates p53/caspase 3 axis
Sinoporphyrin sodium based sonodynamic therapy induces anti-tumor effects in hepatocellular carcinoma and activates p53/caspase 3 axis
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基于华卟啉钠的声动力疗法诱导肝细胞癌的抗肿瘤作用并激活 p53/caspase 3 轴
DOI：
10.1016/j.biocel.2019.01.009
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Cao, Wenwu
中科院分区：
文献类型：
--
作者：
Li, Enze;Sun, Yi;Cao, Wenwu
声动力学疗法（SDT）是一种通过使用低强度超声激活某些化学增敏剂的非侵入性治疗方法。本研究旨在探讨中卟啉钠（DVDMS）介导的SDT（DVDMS-SDT）对肝癌细胞株的体内外抗肿瘤作用。结果表明，DVDMS-SDT在处理肝细胞系Hep-G2中比PpIX-SDT显著更有效。DVDMS-SDT还可增加G2/M期细胞比例，降低CDK 1和Cyclin B1蛋白水平。DVDMS-SDT在体外能显著增加细胞内活性氧自由基（ROS）。ROS的增加上调了p53和Bax的表达，下调了Bcl-2的表达，从而激活了caspase-3，最终导致细胞凋亡。ROS清除剂N-乙酰半胱氨酸（NAC）可部分逆转上述作用。体内实验表明，DVDMS-SDT能有效抑制肿瘤生长，延长荷瘤小鼠的生存时间。更重要的是，没有观察到明显的副作用迹象。结果表明，DVDMS-SDT治疗肝癌疗效确切，无明显毒副作用。SDT的主要机制是由于活性氧增加激活了细胞凋亡的p53/Caspase 3轴。
Sonodynamic therapy (SDT) is a noninvasive therapeutic method via the activation of certain chemical sensitizers using low intensity ultrasound. In this work, we evaluated the antitumor effect of sinoporphyrin sodium (DVDMS) mediated SDT (DVDMS-SDT) on Hepatocellular carcinoma (HCC) cell lines both in vitro and in vivo. The results indicated that DVDMS-SDT was significantly more efficacious than PpIX-SDT in treating hepatocellular cell line Hep-G2. DVDMS-SDT also increased the ratio of cells in the G2/M phase and decreased the CDK1 and Cyclin B1 protein level. DVDMS-SDT markedly increased intracellular reactive oxygen species (ROS) in vitro. The increased ROS production up-regulated the expression of p53 and Bax, and down-regulated Bcl-2 expression, which led to the activation of caspase-3, ultimately initiated cell apoptosis. These effects could be partially reversed by the ROS scavenger N-acetylcysteine (NAC). In vivo experiments revealed that the DVDMS-SDT resulted in an effective inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. More importantly, no obvious signs of side effects were observed. These results suggested that DVDMS-SDT is very effective in treating Hepatocellular carcinoma without side effects. The primary mechanism of SDT is due to the increased ROS activated the p53/Caspase 3 axis of apoptosis.