Resveratrol regulates CXCR4 expression and downstream signaling of Caki-1 cells in vivo and in vitro

Abstract

[한글]

[영문]

Resveratrol, a phytoestrogen found in food products such as grapes and wine, produces various physiological effects. Resveratrol possesses anticancer activity: it inhibits proliferation and induces apoptotic cell death in multiple cancers cells. The chemokine stromal cell-derived factor-1α (SDF-1α)/CXCR4 axis plays a prominent role in tumorigenesis and promotes angiogenesis and migration of tumor cells to metastatic sites in many cancers. Expression of CXCR4 was shown to be upregulated in most renal cell carcinoma (RCC) patients. In human RCC, CXCR4 plays a major role in the proliferation and growth of cancer cells through activation of PI3K/AKT signaling. We demonstrate that resveratrol suppresses the expression of CXCR4, and inhibits cell proliferation and growth of the human kidney cancer cell line, Caki-1. We show that resveratrol suppresses RNA and protein expression of CXCR4 in Caki-1 cells by a mechanism involving transcriptional regulation. Recombinant SDF-1α, the ligand of CXCR4, induces cell proliferation and AKT and extracellular signal?regulated kinase(ERK) 1/2 activation, and can, independently, cause renal cell carcinoma cells proliferation. Resveratrol inhibits cell growth and proliferation caused by SDF-1α in Caki-1 cells. Also, we examined the therapeutic efficacy of resveratrol in vivo by treating SCID mice bearing Caki-1 cells. Resveratrol suppressed both tumor growth and the expression of CXCR4 in the xenograft model. These data suggest that resveratrol may be a therapeutic agent for kidney cancer as an effective inhibitor of CXCR4. These results may provide a new therapeutic strategy for the use of a natural compound in the treatment of human kidney cancer.