Abstract
Primary gastric cancer (PGC) is the fourth most common malignant human cancer and the second leading cause of death worldwide. The majority of the subjects of PGC is diagnosed at a late stage, resulting in poor prognosis and therapeutic outcome, largely attributable to dissemination of tumor cells into circulation as circulating tumor cells (CTCs) and their formation of distal tumor. Curcumin is an active ingredient from the rhizome of the plant Curcuma longa. Here, we assessed whether treatment with Curcumin may reduce the incidence of metastatic tumor formation in liver in mice carrying PGC. We found that Curcumin treatment significantly reduced the presence of CTCs and formation of liver tumor. Mechanistically, Curcumin reduced CXCR4 expression in PGCs in vitro and in vivo, and thus likely inhibited metastasis of PGC through suppression of stromal cell -derived factor-1/CXCR4 signaling. Thus, our study suggests that Curcumin may inhibit liver metastasis of PGC through reducing CTCs.
Highlights
Gastric cancer (GC) is the fourth most common malignant human cancer and the second leading cause of death worldwide [1]
A pooled primary gastric cancer (PGC) cell fraction was prepared from 10 mice that successfully generated tumor, after a negative selection for CD45+ inflammatory cells, and CD31+ tumor endothelial cells (Figure 1C)
(expression of gastrin under insulin promoter) transgenic mice, after which gastric tumor tissue was confirmed by histology after dissection out the formed tumor. (B) Representative histology of normal stomach and GC. (C) A pooled primary gastric cancer (PGC) cell fraction was prepared from 10 mice that successfully generated tumor, after a negative selection for CD45+ inflammatory cells, and CD31+ tumor endothelial cells
Summary
Gastric cancer (GC) is the fourth most common malignant human cancer and the second leading cause of death worldwide [1]. We assessed whether treatment with Curcumin may reduce the incidence of metastatic tumor formation in liver in mice carrying primary GC. A pooled primary gastric cancer cell (PGC) fraction was prepared from 10 mice that successfully generated tumor These PGCs were transduced with a lentivirus carrying luciferase and GFP reporters under a ubiquitous cytomegalovirus promoter to allow visualizetion of the transduced cells in vivo, as well as distinguishing and separation of the transduced cells after transplanted into NOD/SCID mice. The PGCs were subcutaneously grafted into NOD/SCID mice to generate xenografted tumor, after which presence of CTCs in the circulation was assessed by flow cytometry for GFP, and formation of metastatic tumor in liver was examined by bioluminescence assay, 12 weeks after transplantation in mice with or without Curcumin treatment. Our results suggest that Curcumin may inhibit liver metastasis of GC through reducing CTCs
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