Nanosecond pulsed electric field inhibits cancer growth followed by alteration in expressions of NF-κB and Wnt/β-catenin signaling molecules.
Cancer remains a leading cause of death worldwide and total number of cases globally is increasing. Novel treatment strategies are therefore desperately required for radical treatment of cancers and long survival of patients. A new technology using high pulsed electric field has emerged from military application into biology and medicine by applying nsPEF as a means to inhibit cancer. However, molecular mechanisms of nsPEF on tumors or cancers are still unclear. In this paper, we found that nsPEF had extensive biological effects in cancers, and clarified its possible molecular mechanisms in vitro and in vivo. It could not only induce cell apoptosis via dependent-mitochondria intrinsic apoptosis pathway that was triggered by imbalance of anti- or pro-apoptosis Bcl-2 family proteins, but also inhibit cell proliferation through repressing NF-κB signaling pathway to reduce expressions of cyclin proteins. Moreover, nsPEF could also inactivate metastasis and invasion in cancer cells by suppressing Wnt/β-Catenin signaling pathway to down-regulating expressions of VEGF and MMPs family proteins. More importantly, nsPEF could function safely and effectively as an anti-cancer therapy through inducing tumor cell apoptosis, destroying tumor microenvironment, and depressing angiogenesis in tumor tissue in vivo. These findings may provide a creative and effective therapeutic strategy for cancers.
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China ; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Zhigang
Z
Ren
Xinhua
X
Chen
Guangying
G
Cui
Shengyong
S
Yin
Luyan
L
Chen
Jianwen
J
Jiang
Zhenhua
Z
Hu
Haiyang
H
Xie
Shusen
S
Zheng
Lin
L
Zhou
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000628:therapy; D061208:Pulsed Radiofrequency Treatment; D015398:Signal Transduction; D047368:Tumor Burden / Q000528:radiation effects; D059016:Tumor Microenvironment / Q000528:radiation effects; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D016328:NF-kappa B; D051153:Wnt Proteins; D051176:beta Catenin