The Society of Surgical Oncology, inc.
The American Society of Breast Surgeons.
Annals of Surgical Oncology

Log in | Register

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

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
Translational Research and Biomarkers
Online First ™ - July , 2019

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.

Add a comment



0 comment(s)

ANNALS ON SOCIAL MEDIA

@AnnSurgOncol 

Join the conversation!

Follow the journal on Twitter and Facebook

Help to expand the reach of the journal to support the research and practice needs of surgical oncologists and their patients.