Tamoxifen Enhances The Anti-cancer Effect Of Cantharidin And Norcantharidin In Pancreatic Cancer Cell Lines

Objective To explore the effects of Tamoxifen、Cantharidin and its derivatives onthe growth of different pancreatic cancer cells. The mechanism involved in the amplifiedthe anti-cancer effect of Cantharidin and Norcantharidin by Tamoxifen was alsoinvestigated. Methods1. Proliferation was determined by MTT (3-[4,5-dimethyltiazol-2-yl]2,5-diphenyltetrazo-lium bromide).2. The expression level of ERα and ERβ in different pancreatic cancer cell lines weredetermined by RT-PCR.3. The protein expression of PKCα and p-PKCα was tested in pancreatic cancer celllines using Western blotting.Results1. Tamoxifen repressed cell growth in a dose-and time-dependent manner, not only inthe hormone receptors positive cell line, but also in the hormone receptors negative cellslines.2. Cantharidin and Norcantharidin efficiently inhibited the growth of pancreaticcancer cells in a dose-and time-dependent manner.3. Combination of Tamoxifen strengthened the cytotoxicity of Cantharidin orNorcantharidin, presenting synergistic effects.4. Repression on PKC by Tamoxifen was confirmed by using western blot.5. The time-dependent repression on cell viability induced by Tamoxifen could beattenuated by pretreatment with GF109203X, an inhibitor of PKC.6. Treatment with PP2A inhibitors induced the phosphorylation of PKC.7. Both Cantharidin and Norcantharidin induced persistent and excessivephosphorylation of PKCα, which could be repressed by pretreatment with Tamoxifen. Conclusion In our study, we have proved that Tamoxifen and PP2A inhibitors allcould repress the growth of different pancreatic cancer cells, and Tamoxifen strengthenedthe cytotoxicity of Cantharidin and Norcantharidin in pancreatic cancer cells. Itsmechanism is Tamoxifen repressed the phosphorylation of PKC triggered by Cantharidinand Norcantharidin.