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Substance P Promotes the Progression of Endometrial Adenocarcinoma
  1. Jing Ma, MD,
  2. Shifa Yuan, MD,
  3. Jianxin Cheng, MD,
  4. Shan Kang, MD,
  5. Wenhong Zhao, MD and
  6. Jie Zhang, MD
  1. * Department of Gynecology, The Fourth Hospital, Hebei Medical University;
  2. Department of Surgery, Hospital of Hebei Province Crop of Chinese Armed Police Force; and
  3. Department of Traditional Chinese Medicine, The Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei, China.
  1. Address correspondence and reprint requests to Jianxin Cheng, MD, Department of Gynecology, The Fourth Hospital, Hebei Medical University, Shijiazhuang 050011, Hebei, China. E-mail: jianxin_cheng{at}263.net.

Abstract

Objectives It has been demonstrated that substance P (SP) promotes while neurokinin-1 receptor (NK-1R) antagonist inhibits the proliferation of several human cancer cells. Currently, it is still unknown whether such actions exist in human endometrial carcinoma. This study aimed to explore the role of SP/NK-1R signaling in the progression of endometrial adenocarcinoma.

Materials and Methods The expression levels of SP and NK-1R in endometrial adenocarcinoma tissues and Ishikawa cell line were detected by real-time quantitative PCR and Western blot analysis. The effects of SP on Ishikawa cells proliferation and invasion were analyzed using MTT assay and transwell matrigel invasion assay, respectively. The expression levels of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor C (VEGF-C) in Ishikawa cells after administration of SP were detected by real-time quantitative RCR and Western blot analysis.

Results The expression levels of SP and NK-1R were significantly higher in endometrial adenocarcinoma tissues and Ishikawa cells than in normal endometrium. Substance P significantly enhanced the proliferation and invasion of Ishikawa cells. In addition, SP induced the expression of MMP-9 and VEGF-C in Ishikawa cells, whereas NK-1R antagonist inhibited these effects.

Conclusions Substance P plays an important role in the development of endometrial carcinoma by inducing the expression of MMP-9 and VEGF-C and promoting cancer cell proliferation and metastasis, which can be blocked by NK-1R antagonist.

  • Substance P
  • NK-1 receptor
  • Endometrial adenocarcinoma
  • VEGF-C
  • MMP-9

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Footnotes

  • The authors declare no conflicts of interest.