School of Electrical Engineering, Chongqing University, Chongqing 400033, China; Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA.
Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; College of Electrical Engineering and Control Science, Nanjing Tech. University, Nanjing 211816, China.
Bioelectrochemistry. 2021 Dec;142:107942. doi: 10.1016/j.bioelechem.2021.107942. Epub 2021 Aug 31.
Nanosecond pulsed electric fields (nsPEFs) may induce differential effects on tumor cells from different disease stages and could be suitable for treating tumors by preferentially targeting the late-stage/highly aggressive tumor cells. In this study, we investigated the nsPEF responses of mouse ovarian surface epithelial (MOSE) cells representing progressive ovarian cancer from benign to malignant stages and highly aggressive tumor-initiating-like cells. We established the cell-seeded 3D collagen scaffolds cultured with or without Nocodazole (eliminating the influence of cell proliferation on ablation outcome) to observe the ablation effects at 3 h and 24 h after treatment and compared the corresponding thresholds obtained by numerically calculated electric field distribution. The results showed that nsPEFs induced larger ablation areas with lower thresholds as the cell progress from benign, malignant to a highly aggressive phenotype. This differential effect was not affected by the different doubling times of the cells, as apparent by similar ablation induction after a synergistic treatment of nsPEFs and Nocodazole. The result suggests that nsPEFs could induce preferential ablation effects on highly aggressive and malignant ovarian cancer cells than their benign counterparts. This study provides an experimental basis for the research on killing malignant tumor cells via electrical treatments and may have clinical implications for treating tumors and preventing tumor recurrence after treatment.
纳秒级脉冲电场(nsPEFs)可能对来自不同疾病阶段的肿瘤细胞产生不同的影响,并且可以通过优先靶向晚期/高度侵袭性肿瘤细胞来适用于治疗肿瘤。在这项研究中,我们研究了代表良性至恶性阶段渐进性卵巢癌的小鼠卵巢表面上皮(MOSE)细胞和高度侵袭性肿瘤起始样细胞对 nsPEF 的反应。我们建立了细胞接种的 3D 胶原支架培养物,有或没有诺考达唑(消除细胞增殖对消融结果的影响),以观察治疗后 3 小时和 24 小时的消融效果,并比较通过数值计算电场分布获得的相应阈值。结果表明,随着细胞从良性、恶性到高度侵袭性表型的进展,nsPEFs 诱导更大的消融区域,所需的阈值更低。这种差异效应不受细胞倍增时间的影响,因为 nsPEFs 和诺考达唑协同处理后,消融诱导也相似。结果表明,nsPEFs 可以对高度侵袭性和恶性卵巢癌细胞产生优先的消融效果,而对良性细胞则没有。这项研究为通过电疗杀死恶性肿瘤细胞的研究提供了实验基础,并可能对治疗肿瘤和预防治疗后肿瘤复发具有临床意义。