Bekeschus Sander, Käding André, Schröder Tim, Wende Kristian, Hackbarth Christine, Liedtke Kim R, van der Linde Julia, von Woedtke Thomas, Heidecke Claus-Dieter, Partecke Lars-Ivo
Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
Department of General, Visceral, Thoracic and Vascular Surgery, University Medicine Greifswald, Ferdinand- Sauerbruch-Straße, 17475 Greifswald, Germany.
Anticancer Agents Med Chem. 2018;18(6):824-831. doi: 10.2174/1871520618666180507130243.
Cold physical plasma has been suggested as a new anticancer tool recently. However, direct use of plasma is limited to visible tumors and in some clinical situations, is not feasible. This includes repetitive treatment of peritoneal metastases, which commonly occur in advanced gastrointestinal cancer and in pancreatic cancer in particular. In case of diffuse intraperitoneal metastatic spread, Hyperthermic Intraperitoneal Intraoperative Chemotherapy (HIPEC) is used as a therapeutic approach. Plasma-treated solutions may combine non-toxic characteristics with the anticancer effects of HIPEC. Previous work has provided evidence for an anticancer efficacy of plasma-treated cell culture medium but the clinical relevance of such an approach is low due to its complex formulation and lack of medical accreditation.
Plasma-treated Phosphate-Buffered Saline (PBS), which closely resembles medically certified solutions, was investigated for its cytotoxic effect on 2D monolayer murine pancreatic cancer cells in vitro.
Toxicity studies of primary murine fibroblasts, PDA6606 murine pancreatic cancer cells, and COLO 357 human pancreatic cancer cells exposed to plasma-treated PBS were performed.
Plasma-treated PBS significantly decreased cancer cell metabolisms and proliferation whereas plasma-treated Dulbecco's Modified Eagle Medium had no effect. Moreover, tumor cell growth attenuation was significantly higher when compared to syngeneic primary murine fibroblasts. Both results were confirmed in a human pancreatic cancer cell line. Finally, plasma-treated PBS also decreased the size of pancreatic tumors in a three-dimensional manner, and induction of apoptosis was found to be responsible for all anticancer effects identified.
Plasma-treated PBS inhibited cell growth in 2D and 3D models of cancer. These results may help facilitate the development of new plasma-derived anticancer agent with clinical relevance in the future.
冷物理等离子体最近被认为是一种新的抗癌工具。然而,等离子体的直接应用仅限于可见肿瘤,并且在某些临床情况下不可行。这包括对腹膜转移瘤的重复治疗,腹膜转移瘤常见于晚期胃肠道癌,尤其是胰腺癌。在弥漫性腹膜内转移扩散的情况下,术中腹腔内热化疗(HIPEC)被用作一种治疗方法。经等离子体处理的溶液可能将无毒特性与HIPEC的抗癌作用相结合。先前的研究已经证明经等离子体处理的细胞培养基具有抗癌功效,但由于其复杂的配方和缺乏医学认证,这种方法的临床相关性较低。
研究经等离子体处理的磷酸盐缓冲盐水(PBS)对二维单层小鼠胰腺癌细胞的体外细胞毒性作用,该PBS与医学认证溶液非常相似。
对暴露于经等离子体处理的PBS的原代小鼠成纤维细胞、PDA6606小鼠胰腺癌细胞和COLO 357人胰腺癌细胞进行毒性研究。
经等离子体处理的PBS显著降低癌细胞的代谢和增殖,而经等离子体处理的杜氏改良 Eagle培养基则无此作用。此外,与同基因原代小鼠成纤维细胞相比,肿瘤细胞生长的减弱更为显著。这两个结果在人胰腺癌细胞系中得到了证实。最后,经等离子体处理的PBS还以三维方式减小了胰腺肿瘤的大小,并且发现凋亡的诱导是所有已确定的抗癌作用的原因。
经等离子体处理的PBS在二维和三维癌症模型中均抑制细胞生长。这些结果可能有助于促进未来具有临床相关性的新型等离子体衍生抗癌剂的开发。