[Parecoxib sodium down-regulates CXCL8-CXCR1/2 to improve inflammatory microenvironment and promote patient recovery following laparoscopic radical resection of rectal cancer]

Nan Fang Yi Ke Da Xue Xue Bao. 2024 Feb 20;44(2):363-369. doi: 10.12122/j.issn.1673-4254.2024.02.19.
[Article in Chinese]

Abstract

Objective: To study the effect of parecoxib sodium on tumor microenvironment in patients undergoing laparoscopic radical resection of rectal cancer.

Methods: Sixty patients undergoing laparoscopic surgery for radical rectal cancer resection were randomized into test group and control group (n=30). The patients in test control group received intravenous injections of 40 mg parecoxib sodium at the time of anesthesia induction, immediately after and at 12 h after the surgery, and those in the control group were injected with an equal volume of physiological saline at the same time points. Plasma levels of IL-6, TNF-α, and CXCL8 of the patients were measured using ELISA, and expressions of CXCL8, CXCR1, and CXCR2 in the peripheral blood mononuclear cells (PBMCs) were detected with Western blotting. Postoperative VAS scores and gastrointestinal reactions and disease regression at 6 months after the operation were recorded.

Results: Compared with the control patients, the patients in the test group showed significantly reduced plasma levels of IL-6, TNF-α, and CXCL8 (P < 0.05) and milder elevations of CXCL8, CXCR1, and CXCR2 proteins in PBMCs (P < 0.05) with significantly lower VAS scores at 12 h and 24 h after the operation (P < 0.05) and lower postoperative incidence of adverse gastrointestinal reactions (P < 0.05). At 6 months after the operation, the number of patients with metastasis or tumor recurrence was significantly smaller in the test group than in the control group (P>0.05).

Conclusion: Parecoxib sodium can improve the inflammatory microenvironment to promote patient recovery after laparoscopic radical resection of rectal cancer possibly through a mechanism that down-regulates CXCL8-CXCR1/2 expressions in the PBMCs.

目的: 研究帕瑞昔布钠对腹腔镜下直肠癌根治术患者肿瘤微环境的影响。

方法: 选取符合纳入标准的腹腔镜下直肠癌根治术患者60例,随机分成试验组(n=30)和对照组(n=30),对照组患者于麻醉诱导时、术后即刻、术后12 h静脉注射帕瑞昔布钠40mg;试验组患者于同样时间点静脉注射等容量的生理盐水。ELISA检测患者血浆中IL-6,TNF-α,CXCL8含量;Western blot检测患者血样外周血单个核细胞(PBMCs)中CXCL8,CXCR1和CXCR2蛋白表达;记录患者术后VAS评分、术后胃肠道不良反应、术后6个月后患者疾病转归情况。

结果: 与试验组相比,对照组患者血浆中IL-6、TNF-α、CXCL8含量均显著减少(P < 0.05),患者血样外周血单个核细胞(PBMCs)中CXCL8,CXCR1,CXCR2蛋白表达的上调程度均降低(P < 0.05);与试验组相比,对照组于术后12 h、术后24 h VAS评分显著降低(P < 0.05),术后发生胃肠道不良反应发生率显著下降(P < 0.05);在肿瘤发生发展随访结果上,试验组发生转移或复发的患者例数高于对照组(P>0.05)。

结论: 帕瑞昔布钠能改善腹腔镜下直肠癌根治术患者炎症微环境促进患者恢复,其机制可能与下调CXCL8-CXCR1/2表达有关。

Keywords: chemokines; inflammation; parecoxib; peripheral blood mononuclear cells; rectal cancer.

Publication types

  • Randomized Controlled Trial
  • English Abstract

MeSH terms

  • Humans
  • Interleukin-6
  • Isoxazoles*
  • Laparoscopy*
  • Leukocytes, Mononuclear
  • Neoplasm Recurrence, Local
  • Pain, Postoperative
  • Rectal Neoplasms* / surgery
  • Tumor Microenvironment
  • Tumor Necrosis Factor-alpha

Substances

  • parecoxib
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Isoxazoles

Grants and funding

安徽省卫生健康科研项目(AHWJ2022b024):蚌埠医学院研究生科研创新计划项目(Byycx22102)