Fluorouracil regulates VHL/HIF signaling pathway and inhibits proliferation, invasion and metastasis of renal carcinoma cells

doi:10.12092/j.issn.1009-2501.2019.08.005

Abstract

Abstract:

AIM: To investigate the effect of fluorouracil on the proliferation, invasion and metastasis of renal cell carcinoma by regulating VHL/HIF signaling pathway. METHODS: Human kidney cancer 786-0 cells were cultured in vitro. Renal cancer cells were treated with fluorouracil with final concentrations of 6, 60, and 600 μg/mL, respectively. Effects of fluorouracil against kidney cancer cells proliferation was detected by MTT assay. Scratch test was applied to detect the effect of fluorouracil on the metastasis capacity of renal cell carcinoma, and Transwell assay to detect the effect of uracil on the invasion ability of renal cell carcinoma in vitro. Western blot analyzed the VHL/HIF signaling pathway-associated protein HIF-1α, VEGF, activated cysteine-containing aspartate proteinase 3 (Cleaved Caspase-3), matrix metalloproteinases in renal cell carcinoma cells treated with fluorouracil and the effect of 9 (MMP-9) expression. After transfection of pcDNA-HIF-1α by the cell transfection method, the transfection efficiency was detected by Western blot, and the same method was used to examine the effect on the proliferation, invasion and metastasis of renal cell carcinoma.RESULTS:The proliferation of renal cell carcinoma cells treated with fluorouracil was significantly inhibited, and the invasion and metastasis ability was significantly decreased, and it was time-and concentration-dependent (P<0.05). The expression of related proteins HIF-1α, VEGF, and MMP-9 was down-regulated, and Cleaved Caspase-3 the expression was up-regulated. After transfected with pcDNA-HIF-1α, the expression of HIF-1α is upregulated. The proliferation activity and invasion and metastasis ability of renal cell carcinoma were weakened. Compared with the control group, the difference was statistically significant (P<0.05). CONCLUSION:Fluorouracil can inhibit the proliferation, invasion and metastasis of renal cancer cells, and its mechanism is related to blocking the VHL/HIF signaling pathway and regulating the expression of Cleaved Caspase-3 and MMP-9.

Key words: VHL/HIF signaling pathway, renal cancer cells, proliferation, invasion, metastasis

CLC Number:

R965.2

ZHOU Qingying, XU Naifen, ZHENG Dingqin, PAN Qizhuang, ZHANG Zhigang, WANG Shuo. Fluorouracil regulates VHL/HIF signaling pathway and inhibits proliferation, invasion and metastasis of renal carcinoma cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(8): 872-879.

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