Abstract

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.

Highlights

  • Cancer are still a leading cause of death worldwide and accounted for 7.6 million deaths in 2008 according to WHO, and deaths from cancer are projected to rise to over 11 million in 2030 [1]

  • The results proved that nanosecond pulse electric field (nsPEF) could induce apoptosis in various cancer cell lines in vitro [9,10] and a fibrosarcoma tumor ex vivo [7], and eradicate B16f10 melanoma tumor in vivo [11,12,13]

  • As a relatively new technology to interpret cancer, nsPEF is effective in various cell lines in vitro [5,9,10], and B16f10 melanoma and hepatocellular carcinoma [11,24], as well as human pancreatic carcinoma [25] in vivo, demonstrating potential application prospect of nsPEF for cancer therapy

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Summary

Introduction

Cancer are still a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008 according to WHO, and deaths from cancer are projected to rise to over 11 million in 2030 [1]. A significant proportion of cancers can be cured by surgery, radiotherapy or chemotherapy, especially if they are detected early. Some kinds of cancers cannot be discovered in early stage and have little response to radiotherapy and chemotherapy, patients with such cancers have a poor prognosis. Pancreatic cancer has approximately 23% 1-year survival after diagnosis and 5% 5-year survival at best [2]. There were an estimated 43,140 new cases and. 36, 800 deaths attributed to pancreatic cancer in the United States [3,4]. It is essential to search for a new therapy technique to improve prognosis and survival of cancer patients

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