Antitumor And Mechanism Of Thalidomide

Thalidomide was prescribed as a sedative and antiemetic for morning sickness, recent studies showed that thalidomide had antitumor action, but the reported effects varied in tumor treatment, the aim of this study is to explore antitumor and mechanism of thalidomide. In vitro the inhibitory effect of thalidomide on tumor was related to cancer type, its IC50 for MCF-7,HepG-2 and HL-60 were 21.23,30.20,37.29μM respectively with being able to reverse myleran-resistant HL-60. Thalidomide had a little effect on growth of HeLa cells, even at the dose of 300μM the inhibitory rate was only 45.47%, but bcl-2 expressing transfected in HeLa cells enhanced sensitivity to thalidomide, while it promoted resistance of HeLa cells to H₂O₂. In murine implanted tumor, thalidomide could inhibit growth of solid S₁₈₀,H₂₂ and Lewis lung carcinoma in a dose-dependent manner, though the life span of mouse bearing ascitic S₁₈₀ and H₂₂ had no difference between control and thalidomide treatment, thalidomide acted synergistically with cyclophosphamide in antitumor and might decrease dose of cyclophosphamide,which was same as in solid tumor. In xenograft of human cancer on nude mice, in spite of significantly reduction of intratumoral microvessel density (MVD) after thalidomide treatment, thalidomide might prevent OVCAR-3 growing in a dose-dependent manner but had no effect on HCT-8. Thalidomide was able to inhibit angiogenesis in the cultured vascular endothelial cells and the chicken embryo chorioallantoic membrane, its IC₅₀ for HUVEC and ECV-304 were 22.54,31.84μM respectively, the effect on angiogenesis enhanced with the dose increasing of thalidomide. Thalidomide might alleviate acute inflammation induced by egg white ,subacute inflammation induced by cotton ball and chronic inflammation induced by complete Freund's adjuvant in rats; heighten the delayed type hypersensitivity in a dose-dependent manner; promote the clearance of charcoal particles and lymphocyte proliferation at low dose but reduce both of them at high dose. The cause analysis of sensitivity to thalidomide displayed that the antitumor of thalidomide was associated with COX-2 expressing in tumor independent of antiangiogenesis. Thalidomide might induce apoptosis in vascular endothelial cells observed through electron microscope and in HepG-2 cells examined by flow cytometry. Further study on mechanism...