Research on Growth and Metastatic Mechanism of Curcumol on Human Breast Cancer Cell Line MCF-7 in Hypoxic Microenvironment
Objective In this study,the effect of curcumol on the proliferative activity of human breast cancer cell line MCF-7 in a hypoxic microenvironment was investigated with breast cancer as the research object.The effect of curcumol on the growth and metastatic mechanism of MCF-7 cells in a hypoxic microenvironment was further investigated through the expression of tumor growth promoting metastatic factors[hypoxia inducible factor-1α(HIF-1α),C-X-C chemokine receptor type 4(CX-CR4)and Chemokine(C-X-C Motif)Ligand 12(CXCL12)]at the level of mRNA and protein.Methods The proliferative ac-tivity of MCF-7 cells was measured by MTT assay under normoxic conditions with different concentrations of curcumol,and the effects of curcumol on the mRNA expressions of HIF-1α,CXCL1 and CXCR4 in human breast cancer cell line MCF-7 under hypoxic and normoxic environments were detected by RT-PCR,and the mRNA expressions of HIF-1α,CXCL12 and CXCR4 in human breast cancer cell line MCF-7 were detected by Western blot.The effect of curcumol on protein expressions of HIF-1α,CXCL12 and CXCR4 in MCF-7 cells under hypoxia and normoxia was detected by blotting.Immunohistochemistry method was performed to detect the effects of curcumol on the protein expression of HIF-1α,CXCL12 and CXCR4 in MCF-7 under hy-poxia and normoxia.Results Curcumol significantly inhibited the value-added of human breast cancer cell line MCF-7 cells,and the longer the duration of drug action and the higher the concentration,the higher the inhibition rate(P＜0.05).The mRNA and protein expression of HIF-1α:There was almost no expression of HIF-1 α under the condition of normoxia,and the expres-sion of HIF-1α was obvious under the condition of hypoxia,and the expression of mRNA and protein in the hypoxia dosing group treated with curcumol was less than that in the hypoxia control group.The expression was less than that of the anoxic control group(P＜0.05).The immunohistochemical results showed that HIF-1α was mainly expressed in the nucleus of MCF-7.The mRNA and protein expressions of CXCR4 and CXCL12 were significantly higher in the anoxic condition than those in the normox-ic condition(P＜0.05),and the mRNA and protein expressions of CXCR4 and CXCL12 were significantly lower in the anoxic group compared to those in the normoxic group after curcuminoxaline administration(P＜0.05).CXCR4 was mainly expressed in the cytoplasm and cytosol of MCF-7 cells(P＜0.05).CXCR4 was mainly expressed in the cytosol and cytoplasm of MCF-7 cells,and CXCL12 was mainly expressed in the cytosol and cytoplasm of MCF-7 cells.Conclusions Curcumol inhibited the val-ue-added of human breast cancer cell line MCF-7 cells in a concentration-and time-gradient-dependent manner.HIF-1α expression increased under the induction of hypoxic conditions,and the expressions of CXCR4 and CXCL12 factors were up-regulated through the increase of HIF-1α.Curcumol significantly inhibited the expressions of HIF-1α,CXCL12 and CXCR4 factors,and the inhibitory ability of curcumol was stronger under anoxic conditions.
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