摘要
Objective: To investigate the anti-proliferation effect and mechanism of zoledronic acid(ZOL) on human colon cancer line SW480. Methods: SW480 cells were treated with 0, 12.5, 25, 50, 100 and 200 μmo L/L of ZOL for 48 h, and CCK-8 assay was employed to obtain the survival rate of SW480 cells. SW480 cells were treated with 25 μmo L/L of ZOL for 0, 12, 24, 48 and 72 h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25 μmo L/L of ZOL for 48 h, while cells of the Cs A+ZOL group were pretreated with 10 μmo L/L of Cs A for 0.5 h and then treated with 25 μmo L/L of ZOL for 48 h. Then the survival rates of SW480 cells of the control group, ZOL group and Cs A+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. Results: ZOL inhibited the proliferation of SW480 cells, 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 Cs A+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). Conclusions: ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480 cells 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.
Objective: To investigate the anti-proliferation effect and mechanism of zoledronic acid (ZOL) on human colon cancer line SW480. Methods: SW480 cells were treated with 0, 12.5, 25, 50, 100 and 200 mu moL/L of ZOL for 48 h, and CCK-8 assay was employed to obtain the survival rate of SW480 cells. SW480 cells were treated with 25 mu moL/L of ZOL for 0, 12, 24, 48 and 72 h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25 mu moL/L of ZOL for 48 h, while cells of the CsA+ZOL group were pretreated with 10 mu moL/L of CsA for 0.5 h and then treated with 25 mu moL/L of ZOL for 48 h. Then the survival rates of SW480 cells of the control group, ZOL group and CsA+ZOL group were determined. Flow cytometry was employed to detect the apoptosis rate and the mitochondria] transmembrane potential (Delta Psi m) of the three groups and Western blot was used to detect the expressions of cyt C in the cytosol of the three groups. Results: ZOL inhibited the proliferation of SW480 cells, and the inhibition rate positively correlated with the concentration of ZOL and the action time (P < 0.01). The cell survival rate and the Delta Psi m 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 Delta Psi m 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). Conclusions: ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480 cells directly by opening the mitochondrial permeability transition pore abnormally, decreasing Delta Psi m, and releasing the cyt C into the cytosol. And the effect enhances with the increases of the concentration of ZOL and the action time.
基金
supported by National Natural Science Foundation(NO.81272480)