Thalidomide inhibits growth of tumors through COX-2 degradation independent of antiangiogenesis.

Article Details

Citation

Du GJ, Lin HH, Xu QT, Wang MW

Thalidomide inhibits growth of tumors through COX-2 degradation independent of antiangiogenesis.

Vascul Pharmacol. 2005 Aug;43(2):112-9.

PubMed ID
15982930 [ View in PubMed
]
Abstract

Thalidomide is an antiangiogenic drug and is clinically useful in a number of cancers. However, the molecular mechanism by which thalidomide exerts its antitumor effects is poorly understood. This study was designed to clarify the relationship between antiangiogenesis and antitumor effects of thalidomide and to explore the molecular mechanism for its antitumor activity. We evaluated the effects of thalidomide on the growth of human tumor cells expressing (MCF-7 and HL-60) or not expressing (HeLa and K562) COX-2 in vitro. We also studied the effects of thalidomide on COX-1, COX-2 or bcl-2 expression, TNFalpha, VEGF, GSH and cytochrome c in these cells. Thalidomide could inhibit tumor growth in a concentration-dependent manner in MCF-7 and HL-60; its IC50s for them were 18.36+/-2.34 and 22.14+/-2.15 microM, respectively, while this effect was not observed in HeLa and K562. Thalidomide reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. Moreover, cells not expressing COX-2 were insensitive to the growth-inhibitory and effects on cytokines of thalidomide. In our mouse xenograft model of OVCAR-3 and HCT-8, we found that thalidomide could decrease intratumoral microvessel density in both tumors; it exerted antitumor effects only on OVCAR-3 expressing COX-2 but did not on HCT-8 not expressing COX-2. Effect of thalidomide on COX-1 and COX-2 in vivo was consistent with that of in vitro. These results demonstrated that thalidomide might inhibit growth of tumors through COX-2 degradation independent of antiangiogenesis.

DrugBank Data that Cites this Article

Pharmaco-proteomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
ThalidomideApproved Investigational WithdrawnTNF7124
decreased
Thalidomide results in decreased expression of TNF protein6p21.33
ThalidomideApproved Investigational WithdrawnTNF7124
decreased
Thalidomide results in decreased expression of TNF protein6p21.33
ThalidomideApproved Investigational WithdrawnTNF7124
decreased
Thalidomide results in decreased expression of TNF protein6p21.33
ThalidomideApproved Investigational WithdrawnTNF7124
decreased
Thalidomide results in decreased expression of TNF protein6p21.33