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14.11.2017 | Pancreatic Tumors | Ausgabe 1/2018

Annals of Surgical Oncology 1/2018

Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 1/2018
Autoren:
MD Yusuke Sato, MD, PhD, FACS Suguru Yamada, MD Shigeomi Takeda, MD, PhD Norifumi Hattori, PhD Kae Nakamura, PhD Hiromasa Tanaka, MD, PhD Masaaki Mizuno, PhD Masaru Hori, MD, PhD, FACS Yasuhiro Kodera
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1245/​s10434-017-6239-y) contains supplementary material, which is available to authorized users.

Abstract

Background

The medical applications of nonequilibrium atmospheric pressure plasma in cancer therapy have attracted attention. We previously reported on the antitumor effect of plasma-activated medium. However, this approach requires plasma-activated liquids that are administrable to the human body. In this study, we produced plasma-activated lactated Ringer’s solution (PAL) and evaluated its antitumor effect and mechanism. Furthermore, we evaluated the effect of the intraperitoneal administration of PAL using a peritoneal dissemination mouse tumor model.

Methods

The antitumor effect of PAL on pancreatic cancer cell lines was evaluated using proliferation and apoptosis assays. In addition, cellular reactive oxygen species (ROS) generation was examined. The role of ROS was assessed using a proliferation assay with N-acetyl cysteine (NAC). An adhesion assay was performed to evaluate the effect of PAL on cell adhesion. Finally, pancreatic cancer cells stably expressing luciferase (AsPC-1/CMV-Luc) were injected intraperitoneally into mice, followed by intraperitoneal injection of PAL. Peritoneal dissemination was monitored using in vivo bioluminescent imaging.

Results

The antitumor effect of PAL was shown in all cell lines in vitro. The TUNEL assay showed that PAL induced apoptosis. ROS uptake was observed in PAL-treated cells, and the antitumor effect was inhibited by NAC. Cell adhesion also was suppressed by PAL. The intraperitoneal administration of PAL suppressed the formation of peritoneal nodules in vivo.

Conclusions

Our study demonstrated the antitumor effects of PAL in vitro and in vivo. Intraperitoneal administration of PAL may be a novel therapeutic option for peritoneal metastases.

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Zusatzmaterial
Supplementary Fig. 1 Adhesion assay. A total of 2.5 × 105 floating cells were exposed to PAL, Lactec, or RPMI-1640 for 10 min. After PAL treatment, Lactec or RPMI-1640 was replaced with RPMI-1640, and the cells were seeded on a 96-well collagen-coated plate. One hour later, unattached cells were removed, and the number of adherent cells was estimated using an MTS assay. Assays were performed in triplicate (PPTX 83 kb)
10434_2017_6239_MOESM1_ESM.pptx
Literatur
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