Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma.
Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma.
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基于外原卟啉 IX 的声动力疗法对人口腔鳞状细胞癌的抗增殖和凋亡诱导作用。
DOI：
10.1038/srep40967
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发表时间：
2017-01-19
影响因子：
4.6
通讯作者：
Cao W
中科院分区：
文献类型：
--
作者：
Lv Y;Zheng J;Zhou Q;Jia L;Wang C;Liu N;Zhao H;Ji H;Li B;Cao W
声动力疗法（SDT）是一种创新的癌症治疗方式。但SDT对口腔鳞状细胞癌的生物学效应尚未研究。我们前期的研究表明，基于内原卟啉IX的SDT（ALA-SDT）可以通过线粒体途径诱导人舌鳞状细胞癌SAS细胞凋亡。在此，我们研究了基于外切原卟啉的 SDT (PpIX-SDT) 对 SAS 细胞体外和体内的影响。我们证明，与单独超声处理相比，PpIX-SDT 增加了 G2/M 期细胞的比例，并诱导了 3-4 倍的细胞凋亡。 PpIX-SDT 在线粒体损伤之前引起细胞膜损伤，并上调 Fas 和 Fas L 的表达，而如果细胞用 p53 抑制剂预处理，则该效应会受到抑制。此外，我们还检测了具有不同 p53 状态的两种细胞系中 SDT 诱导的细胞凋亡。 SDT组发现野生型p53 SAS细胞中p53表达和凋亡率增加，而p53突变的HSC-3细胞没有表现出这种增加。我们的数据表明，PpIX-SDT 通过将细胞周期阻滞在 G2/M 期并激活外在 Fas 介导的膜受体途径诱导细胞凋亡（受 p53 调节）来抑制 SAS 细胞的增殖。
Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3–4 times more cell apoptosis compared to sonocation alone. PpIX-SDT caused cell membrane damage prior to mitochondria damage and upregulated the expression of Fas and Fas L, while the effect was suppressed if cells were pre-treated with p53 inhibitor. Additionally, we examined the SDT-induced cell apoptosis in two cell lines with different p53 status. The increases of p53 expression and apoptosis rate in wild-type p53 SAS cells were found in the SDT group, while p53-mutated HSC-3 cells did not show such increase. Our data suggest that PpIX-SDT suppress the proliferation of SAS cells via arresting cell cycle at G2/M phase and activating the extrinsic Fas-mediated membrane receptor pathway to induce apoptosis, which is regulated by p53.