Sinoporphyrin sodium triggered sono-photodynamic effects on breast cancer both in vitro and in vivo
Sinoporphyrin sodium triggered sono-photodynamic effects on breast cancer both in vitro and in vivo
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中华卟啉钠在体外和体内引发对乳腺癌的声光动力效应
DOI：
10.1016/j.ultsonch.2016.01.038
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发表时间：
2016-07-01
影响因子：
8.4
通讯作者：
Wang, Xiaobing
中科院分区：
文献类型：
--
作者：
Liu, Yichen;Wang, Pan;Wang, Xiaobing
声光动力疗法（SPDT）是一种很有前途的抗癌策略。简单地说，SPDT结合超声和光来激活产生机械、声化学和光化学活性的敏化剂。辛卟啉钠（DVDMS）是一种新发现的敏化剂，在声动力和光动力治疗中都显示出巨大的潜力。在本研究中，我们主要通过DVDMS评估SDT和PDT在体外和体内对乳腺癌的联合作用。在体外，通过MIT和菌落形成实验，与单独的SDT或PDT相比，DVDMS-SPDT引起了更严重的细胞毒性。2',7'-二氯二氢荧光素-二乙酸酯（DCFH-DA）和二氢乙啶（DHE）染色显示，联合治疗组细胞内活性氧（ROS）显著增加。对苯二甲酸（TA）法和fd500摄取法反映超声照射后的空化效应和细胞膜通透性改变也参与了联合治疗的增强。在体内，DVDMS-SPDT明显抑制肿瘤体积和肿瘤重量的生长。苏木精-伊红染色和免疫组化分析显示，DVDMS-SPDT能明显抑制肿瘤的增殖。此外，DVDMS-SPDT在高转移性4T1小鼠异种移植模型中显著抑制肿瘤肺转移，这与transwell实验评估的体外结果一致。此外，DVDMS-SPDT对4T1异种移植模型的体重和主要器官无明显影响。结果提示，SDT联合PDT增敏剂DVDMS的治疗效果更好，DVDMS- spdt可能是一种治疗高转移性乳腺癌的潜在策略。(C) 2016 Elsevier B.V.版权所有
Sono-photodynamic therapy (SPDT) is a promising anti-cancer strategy. Briefly, SPDT combines ultrasound and light to activate sensitizers that produce mechanical, sonochemical and photochemical activities. Sinoporphyrin sodium (DVDMS) is a newly identified sensitizer that shows great potential in both sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we primarily evaluated the combined effects of SDT and PDT by using DVDMS on breast cancer both in vitro and in vivo. In vitro, DVDMS-SPDT elicits much serious cytotoxicity compared with either SDT or PDT alone by MIT and colony formation assays. 2',7'-Dichlorodihydrofluo-rescein-diacetate (DCFH-DA) and dihydroethidium (DHE) staining revealed that intracellular reactive oxygen species (ROS) were significantly increased in groups given combined therapy. Terephthalic acid (TA) method and FD500-uptake assay reflected that cavitational effects and cell membrane permeability changes after ultrasound irradiation were also involved in the enhancement of combination therapy. In vivo, DVDMS-SPDT markedly inhibits the tumor volume and tumor weight growth. Hematoxylin-eosin staining and immunohistochemistry analysis show DVDMS-SPDT greatly suppressed tumor proliferation. Further, DVDMS-SPDT significantly inhibits tumor lung metastasis in the highly metastatic 4T1 mouse xenograft model, which is consistent well with the in vitro findings evaluated by transwell assay. Moreover, DVDMS-SPDT did not produces obvious effect on body weight and major organs in 4T1 xenograft model. The results suggest that by combination SDT and PDT, the sensitizer DVDMS would produce much better therapeutic effects, and DVDMS-SPDT may be a potential strategy against highly metastatic breast cancer. (C) 2016 Elsevier B.V. All rights reserved.