The effect of SCF and ouabain on small intestinal motility dysfunction induced by gastric cancer peritoneal metastasis.

Abstract

The interstitial cells of Cajal (ICCs) play an important role in maintaining the normal function of gastrointestinal dynamics. In our previous study, we reported that, in advanced gastric cancer, the frequency of bowel movement is always reduced, due in part to the decreased number of ICCs. To investigate the impact of ICCs in gastric cancer, we established a mouse model of gastric cancer peritoneal metastasis using SGC-7901 gastric adenocarcinoma cells and their supernatant. Then, stem cell factor (SCF) and ouabain were used as therapeutic agents to improve gut dynamics. Our data showed that, compared with the normal mice, treatment with SGC-7901 cells and their supernatant led to a significant reduction of the muscle layer thickness, a decreased number of ICCs, broadened gaps between ICCs and surrounding cells, degeneration and necrosis of smooth muscle cells (SMCs), and infiltration of inflammatory cells. In contrast to SGC-7901 cell and supernatant treatment, SCF intervention caused mild submucosal edema and mitochondrial proliferation in the ICCs and SMCs. Additionally, ouabain treatment led to inflammatory cells infiltration into the submucosa and a decreased volume of ICCs. In conclusion, our data illustrated that, under the condition of gastric cancer peritoneal metastasis, the dysfunction of intestinal peristalsis may be related to pathological changes in ICCs. Moreover, we demonstrated that SCF treatment may help to improve intestinal dynamics by regulating the number and function of ICCs.

• Authors: Dan Kong, Jing Li, Baoshan Zhao, Bairong Xia, Lei Zhang, Yan He, Xiuli Wang, Lei Gao, Yufu Wang, Xiaoming Jin, Ge Lou
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 32 Issue 3 Pg. 267-77 (Mar 2015) ISSN: 1573-7276 [Electronic] Netherlands
• PMID: 25689893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• RNA, Messenger
• Stem Cell Factor
• Ouabain
• Sodium
• Proto-Oncogene Proteins c-kit

Topics

• Adenocarcinoma (drug therapy, metabolism, pathology)
• Animals
• Blotting, Western
• Cardiotonic Agents (pharmacology)
• Combined Modality Therapy
• Disease Models, Animal
• Electrophysiology
• Female
• Gastrointestinal Motility (drug effects)
• Humans
• Interstitial Cells of Cajal (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Nude
• Ouabain (pharmacology)
• Peritoneal Neoplasms (drug therapy, metabolism, secondary)
• Proto-Oncogene Proteins c-kit (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium (blood)
• Stem Cell Factor (pharmacology)
• Stomach Neoplasms (drug therapy, metabolism, pathology)
• Tumor Cells, Cultured