Effect Of Cadmium On Growth Of MCF-7Human Breast Cancer Cell And Its Mechanism

In recent years, the environmental pollution is a growing great problem，because ofthe role in the accumulation of heavy metals and long-term exposure to crops and water inthe environment. It is a serious threat on food safety and human health. Theepidemiological data show that cadmium may be one of the causes of breast cancer. Breastcancer is an estrogen-dependent disease, cadmium as researchers focus on highlyquestionable environmental estrogen-like substances.Objective:MCF-7human breast cancer cells were studied to explore the effect of cadmium oncell growth and its possible mechanism of action.Methods:1. MCF-7cells treated with cadmium, the experimental group selection10^-5,10^-6,10^-7,10^-8,10^-9,10^-10,10^-11,10^-12mol/L eight concentration, each treatment for12h,24h, 48h,72h,96h and use estradiol (10^-9mol/L) as the positive control.The MTT assaydetected cadmium on cell proliferation.2. Using the last step experiments screened relative cell proliferation rate can reach thelargest concentration of cadmium and processing time, while the cells were treatedwith the estrogen receptor antagonist fulvestrant and cadmium, MTT assay wasfurther observed cell proliferation, estradiol was the positive control.3. Cell migration was evaluated by scratches experimental.The cell apoptosis and cellcycle changes are detected by flow cytometry.4. Western-blot detection of estrogen receptor alpha, estrogen receptor β, Akt proteinexpression, and protein expression changes in fulvestrant antagonistic.Results:1. Cadmium can promote the proliferation of MCF-7cells （P <0.05）.The effect on cellproliferation were most obvious by the way of treated with10^-6mol/L for24h and10^-9mol/L for72h, the relative growth rate were133%and138%, positive controlestradiol at various time points can make the cells proliferation significantly; theproliferation of MCF-7treated by cadmium can be blocked by fulvestrant, andestradiol are similar to the cells.2. After cell scratch injury,10^-9mol/L cadmium treat72h can make migration of MCF-7cell significantly enhanced, scratch wound healing rate （25.7±1.96）%, comparedwith the control group was significant higher difference significant （P <0.05）, whilescratch wound healing rate was no significant change after the10^-6mol/L cadmiumMCF-7cells was scratch after24h and72h.3. Treat cadmium of10^-9mol/L for72h significantly inhibited MCF-7cell death, theratio of death cell decreased by16%compared to the control group, the difference wasstatistically significant （P <0.05）. While the ratio of death cell that treat10^-6mol/Lcadmium for24h had no significant effect.4.10^-6mol/L cadmium treatment for72h, and10^-9mol/L cadmium treatment for24h candecrease in the proportion of cells in G1phase and increased the proportion of G2 phase cells, promote the transformation of the cell cycle in MCF-7cellproliferation.10^-6mol/L cadmium treat for24h can make G1phase cell proportiondecreased from the control group （56.42±2.33）%to （51.20±1.95）%, while theproportion of G2phase of the control group from （27.35±1.69%） to （32.06±1.32）%.10^-9mol/L cadmium treat for72h, G1phase cell proportion decreased from the controlgroup （55.39±2.12）%to （50.08±2.06）%, while the G2phase cells from the controlgroup （27.21±2.60）%increased （34.14±2.18）%.5. Use10^-6mol/L cadmium and estradiol treatment MCF-7cells24h could be asignificant increase in ERα protein expression （P <0.05）, while the effect can beblocked by fulvestrant.ERα protein expression was significantly increased by treated10^-9mol/L cadmium for72h and estradiol（P <0.05）.The same effect can also beblocked by fulvestrant; ERβ protein expression in the experimental groups were notsignificantly differences.6. After treat10^-6mol/L cadmium for4h and24h, P-Akt protein expression wassignificantly increased（P <0.05）.Treat10^-9mol/L cadmium for72h also enable P-Aktprotein expression increased（P <0.05）.The effect of cadmium can be blocked byfulvestrant.Estradiol make the same effect with cadmium in the three time points.Conclusion:1. Cadmium can promote MCF-7human breast cancer cell growth cultured in vitro, andbe blocked by estrogen receptor antagonist. At the same time, the low doseintervention cadmium (10^-6mol/L intervention24h) can also enhance the ability ofcell migration, inhibition of cell death, accelerating the transformation of the cellcycle.2. Cadmium can play the estrogen-like effect that have a similar role as estradiol, whichpromote the growth of MCF-7human breast cancer cells through activation of ERαexpression.3. In vitro,cadmium can regulate the PI3K/Akt signaling pathway and activateintracellular signaling cascades reaction, which is the similiar effect of estrogen.