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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2019

01-09-2019 | Translational Research and Biomarkers

Methylprednisolone Inhibits Tumor Growth and Peritoneal Seeding Induced by Surgical Stress and Postoperative Complications

Authors: Yoshiki Taniguchi, MD, Yukinori Kurokawa, MD, PhD, FACS, Takaomi Hagi, MD, Tsuyoshi Takahashi, MD, PhD, FACS, Yasuhiro Miyazaki, MD, PhD, Koji Tanaka, MD, PhD, Tomoki Makino, MD, PhD, Makoto Yamasaki, MD, PhD, Kiyokazu Nakajima, MD, PhD, FACS, Masaki Mori, MD, PhD, FACS, Yuichiro Doki, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2019

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Abstract

Background

Surgery often introduce inflammatory response, which may promote tumor growth and metastasis of residual cancer cells. We investigated the impacts of methylprednisolone on the tumor growth and peritoneal seedings in mice treated with lipopolysaccharide (LPS), which mimics systemic inflammation induced by surgical stress and postoperative complications.

Methods

The serum interleukin-6 (IL-6) levels, tumor volume, tumor weight, and the number of peritoneal nodules were investigated in tumor growth model and peritoneal seeding model using BALB/c mice and murine CT26 cancer cell lines in vivo. We conducted functional analyses of IL-6 in Western blotting and proliferation assays in vitro. We also investigated whether preoperative administration of methylprednisolone decreased postoperative serum IL-6 levels in cancer patients in a randomized clinical study.

Results

In the in vivo study, methylprednisolone inhibited the LPS-induced increase of serum IL-6 levels (mean, 33,756 pg/ml vs. 5917 pg/ml; P < 0.001), tumor volume (mean, 397 mm3 vs. 274 mm3; P = 0.019), tumor weight (mean, 0.38 g vs. 0.15 g; P = 0.020), and the number of peritoneal nodules (mean, 112 vs. 47; P = 0.002). In the in vitro study, IL-6 enhanced JAK/STAT signaling and increased the cell proliferation, and IL-6R-neutralizing antibody attenuated these effects. In the clinical study, serum IL-6 levels were significantly decreased by methylprednisolone (median, 97.5 pg/ml vs. 18.0 pg/ml; P = 0.030).

Conclusions

Surgical stress and postoperative complications may enhance tumor growth due to the increase of IL-6. However, methylprednisolone can decrease serum IL-6 levels, thus inhibiting tumor growth and peritoneal seeding.
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Metadata
Title
Methylprednisolone Inhibits Tumor Growth and Peritoneal Seeding Induced by Surgical Stress and Postoperative Complications
Authors
Yoshiki Taniguchi, MD
Yukinori Kurokawa, MD, PhD, FACS
Takaomi Hagi, MD
Tsuyoshi Takahashi, MD, PhD, FACS
Yasuhiro Miyazaki, MD, PhD
Koji Tanaka, MD, PhD
Tomoki Makino, MD, PhD
Makoto Yamasaki, MD, PhD
Kiyokazu Nakajima, MD, PhD, FACS
Masaki Mori, MD, PhD, FACS
Yuichiro Doki, MD, PhD
Publication date
01-09-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 9/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07585-4

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