Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.
Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.
复制标题
体外和体内纳秒电场对肝细胞癌的比较研究表明巨噬细胞浸润有助于体内肿瘤消融
DOI：
10.1371/journal.pone.0086421
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Chen X;Yin S;Hu C;Chen X;Jiang K;Ye S;Feng X;Fan S;Xie H;Zhou L;Zheng S
背景与目的肝细胞癌的复发和转移与预后不良相关，即使在行根治性切除的患者中也是如此。因此，迫切需要有效的治疗来提高患者的生存率。先前，我们报道了纳秒脉冲电场（nsPEFs）可以通过诱导细胞凋亡和抑制血管生成来消融黑色素瘤。本研究旨在通过比较纳秒电场在体内和体外对肝癌的剂量效应，探讨体内消融策略。材料与方法以肝癌细胞系HepG2、SMMC7721、Hep1-6、HCCLM3为实验材料，体外检测100 ns nsPEFs的抗增殖和抗迁移能力。采用人皮下异种移植HCCLM3细胞BALB/c裸鼠动物模型，检测其体内抗肿瘤生长和巨噬细胞浸润情况。结果nsPEFs体外抗肿瘤作用呈剂量依赖性。但体内研究表明，低剂量多药治疗策略优于高剂量单药治疗。多次低剂量nsPEFs处理后，肿瘤内巨噬细胞浸润明显增加。结论低剂量多次应用nsPEFs在体内抑制肿瘤体积的效果优于高剂量单次应用，但与体外剂量效应关系存在较大差异。除了电场强度外，巨噬细胞的参与也必须考虑到体内效应的变异性和毒理学。
Background and Aim Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs) can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. Materials and Methods Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. Results In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. Conclusion The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.
登录
查看更多内容
影响因子：
4.3
作者：
Nuccitelli R;Tran K;Lui K;Huynh J;Athos B;Kreis M;Nuccitelli P;De Fabo EC
通讯作者：
De Fabo EC
影响因子：
2.8
作者：
Chen, X.;Zhuang, J.;Beebe, S. J.
通讯作者：
Beebe, S. J.
影响因子：
1.9
作者：
Schoenbach, KH;Beebe, SJ;Buescher, ES
通讯作者：
Buescher, ES
纳秒脉冲电场治疗后正常皮肤和黑色素瘤的组织病理学
影响因子：
2.2
作者：
Chen X;James Swanson R;Kolb JF;Nuccitelli R;Schoenbach KH
通讯作者：
Schoenbach KH
影响因子：
3.9
作者：
Pakhomov, Andrei G.;Shevin, Rachael;Schoenbach, Karl H.
通讯作者：
Schoenbach, Karl H.