Anti-proliferation effect of zoledronic acid on human colon cancer line SW480.

Abstract

To investigate the anti-proliferation effect and mechanism of zoledronic acid (ZOL) on human colon cancer line SW480. SW480cells were treated with 0, 12.5, 25, 50, 100 and 200μmoL/L of ZOL for 48h, and CCK-8 assay was employed to obtain the survival rate of SW480cells. SW480 cells were treated with 25μmoL/L of ZOL for 0, 12, 24, 48 and 72h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25μmoL/L of ZOL for 48h, while cells of the CsA+ZOL group were pretreated with 10μmoL/L of CsA for 0.5h and then treated with 25μmoL/L of ZOL for 48h. Then the survival rates of SW480cells of the control group, ZOL group and CsA+ZOL group were determined. Flow cytometry was employed to detect the apoptosis rate and the mitochondrial transmembrane potential (△Ψm) of the three groups and Western blot was used to detect the expressions of cyt C in the cytosol of the three groups. ZOL inhibited the proliferation of SW480cells, and the inhibition rate positively correlated with the concentration of ZOL and the action time (P<0.01). The cell survival rate and the △Ψm of the ZOL group were greatly lower than those of the control group, while the apoptosis rate and the expression of cyt C in the cytosol were obviously higher than those of the control group. All the differences showed distinctly statistical significances (P<0.01). The cell survival rate and the △Ψm of the CsA+ZOL group were all lower than those of the control group, but substantially higher than those of the ZOL group; while the apoptosis rate and the expression of cyt C in the cytosol were higher than those of the control group, but distinctly lower than those of the ZOL group. All the differences were statistically significant (P<0.01). ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480cells directly by opening the mitochondrial permeability transition pore abnormally, decreasing △Ψm, and releasing the cyt C into the cytosol. And the effect enhances with the increases of the concentration of ZOL and the action time.