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

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Disclosure

There are no conflicts of interest or financial ties to disclose.

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Yusuke Sato MD, Suguru Yamada MD, PhD, FACS, Shigeomi Takeda MD, Norifumi Hattori MD, PhD & Yasuhiro Kodera MD, PhD, FACS

  2. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kae Nakamura PhD

  3. Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Hiromasa Tanaka PhD & Masaaki Mizuno MD, PhD

  4. Plasma Nanotechnology Research Center, Nagoya University, Nagoya, Japan

    Masaru Hori PhD

Authors
  1. Yusuke Sato MD
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  2. Suguru Yamada MD, PhD, FACS
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  3. Shigeomi Takeda MD
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  4. Norifumi Hattori MD, PhD
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  5. Kae Nakamura PhD
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  6. Hiromasa Tanaka PhD
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  7. Masaaki Mizuno MD, PhD
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  8. Masaru Hori PhD
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  9. Yasuhiro Kodera MD, PhD, FACS
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Corresponding author

Correspondence to Suguru Yamada MD, PhD, FACS.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2017_6239_MOESM1_ESM.pptx

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)

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Sato, Y., Yamada, S., Takeda, S. et al. Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo. Ann Surg Oncol 25, 299–307 (2018). https://doi.org/10.1245/s10434-017-6239-y

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  • DOI: https://doi.org/10.1245/s10434-017-6239-y

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