PO.TB03.01 · 肿瘤生物学
生物场疗法通过调控转移级联的多个步骤抑制胰腺癌侵袭和转移
Biofield therapy inhibits pancreatic cancer invasion and metastasis by modulating multiple steps of metastatic cascade
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
生物场疗法(BTs)作为癌症潜在的补充治疗正日益受到关注。已开发出一些设备来模拟BT从业者发射的能量场或电磁场。我们此前报道,BT在体外和相关动物模型中显著抑制了胰腺癌细胞的生长和侵袭性。为了确定转移级联的哪些步骤受到BT影响,并阐明胰腺导管腺癌(PDAC)中潜在的抗转移机制,我们使用转移性小鼠模型进行了体内研究。在KPCY原位模型中,与集落对照(CC)组和假处理对照(SC)组相比,BT治疗分别显著减少了可见肝结节的百分比61.3%和54.6%(p<0.05)。对肝组织中YFP+细胞的成像显示,相对于CC和SC组,BT组的播散性肿瘤细胞显著减少(p<0.05)。在尾静脉注射模型中,与SC小鼠相比,BT治疗小鼠的肺组织表现出YFP+信号强度显著降低59.6%,支持BT抑制PDAC细胞转移播散的结论。荷有PANC-1原位肿瘤的BT治疗小鼠的肿瘤游离DNA水平(11.5±4.6 ng/μl)显著低于假处理对照(24.7±7.9 ng/μl;p<0.01),提示BT治疗损害肿瘤细胞的血管内渗。这与我们之前的发现一致,即BT抑制人PDAC PANC-1细胞中的EMT。此外,BT在PANC-1细胞中诱导失巢凋亡,表明BT也可能降低PDAC细胞在循环中的存活。为研究BT是否影响转移定植,将PANC-1和KPCY细胞均暴露于BT,并使用鬼笔环肽染色和纤连蛋白定量进行黏附实验,因为纤连蛋白是细胞黏附的关键调节因子。暴露于BT 15分钟的PANC-1细胞每个视野平均有14±4个黏附细胞,而SC组为96±35个(p<0.0001)。同样,基于纤连蛋白的细胞黏附测量显示,相对于SC,BT治疗的PANC-1细胞减少了58.3%(p<0.001)。BT还显著降低了PANC-1细胞中的F-actin强度(p<0.01),在处理30分钟后的KPCY细胞中观察到类似结果。表观遗传谱分析进一步揭示,BT调控了参与肌动蛋白细胞骨架调节的基因表达。总之,这些结果表明,生物场疗法抑制了多个转移步骤,包括细胞侵袭/迁移、血管内渗、循环中存活和定植,最终促成了其在PDAC模型中的抗转移效应。这些过程可能部分通过细胞骨架组织,特别是肌动蛋白动力学的改变来介导。
查看英文原文 English abstract
Biofield therapies (BTs) are gaining attention as potential complementary treatments for cancer. Some devices have been developed to mimic the energetic or electromagnetic fields emitted by BT practitioners. We previously reported that BT significantly inhibited growth and invasiveness of pancreatic cancer cells in vitro and in relevant animal models. To identify which steps of the metastatic cascade are affected by BT and to elucidate potential antimetastatic mechanisms in pancreatic ductal adenocarcinoma (PDAC), we conducted in vivo studies using metastatic mouse models. In a KPCY orthotopic model, BT treatment significantly reduced the percentage of visible liver nodules by 61.3% and 54.6% compared with the colony control (CC) and sham control (SC) groups, respectively (p < 0.05). Imaging of YFP+ cells in the liver tissues revealed a significant reduction in disseminated tumor cells in the BT group relative to CC and SC groups (p < 0.05). In a tail-vein injection model, lung tissues from BT treated mice exhibited a significant 59.6% reduction in YFP+ signal intensity compared with SC mice, supporting the conclusion that BT suppresses metastatic dissemination of PDAC cells. BT treated mice bearing PANC-1 orthotopic tumors had significantly lower levels of tumor cell-free DNA (11.5 ± 4.6 ng/μl) compared with sham control (24.7 ± 7.9 ng/μl; p < 0.01), suggesting that BT treatment impairs tumor cell intravasation. This is consistent with our previous findings that BT inhibits EMT in human PDAC PANC-1 cells. Additionally, BT induced anoikis in PANC-1 cells, indicating that BT may also reduce PDAC cell survival in circulation. To investigate whether BT affects metastatic colonization, both PANC-1 and KPCY cells were exposed to BT and subjected to adhesion assay using phalloidin staining and fibronectin quantification, as fibronectin is a key regulator of cell adhesion. PANC-1 cells exposed to BT for 15 mins showed an average of 14 ± 4 adhered cells per field, compared with 96 ± 35 in the SC group (p < 0.0001). Similarly, fibronectin-based cell adhesion measurements showed a 58.3% decrease in BT-treated PANC-1 cells relative to SC (p < 0.001). BT also significantly reduced F-actin intensity in PANC-1 cells (p < 0.01), with similar results observed in KPCY cells after 30 min of treatment. Epigenetic profiling further revealed that BT modulated the expression of genes involved in actin cytoskeleton regulation. Collectively, these results demonstrated that biofield therapy suppressed multiple metastatic steps including cell invasion/migration, intravasation, survival in circulation, and colonization ultimately contributing to its antimetastatic effects in PDAC models. These processes may be mediated in part through alterations in cytoskeleton organization, particularly actin dynamics.
利益披露 Disclosure
P. Yang, None..
S. Chakraborty, None..
P. Nguyen, None..
D. Deng, None..
A. Eckstrom, None..
A. Cusimano, None..
D. Wei, None..
L. Cohen, None.