Effects of the bile acid UDCA on PDT Efficacy in Vitro and in Vivo

摘要

The phototoxicity of PDT in cell culture can be promoted by the relatively hydrophilic bile acid UDCA (ursodeoxycholic acid). This was attributed to a conformational change in the anti-apoptotic protein Bcl-2, leading to an enhanced sensitivity to photodamage by sensitizers that target sites of Bcl-2 localization. UDCA also promoted the binding and inactivation of Bcl-2 by the non-peptidic antagonist HA14-1, suggesting that UDCA may also be useful for promoting chemotherapy designed to target Bcl-2. In tumor-bearing animals, addition of UDCA to a PDT protocol involving the tin etiopurpurin SnET2 resulted in enhanced cancer control, but there was no effect on the extent of PDT-induced vascular shut-down. These results are consistent with the proposal that UDCA only promotes direct tumor cell kill. In this report, we have summarized recent research relating to mode of action of UDCA as it effects the on the efficacy of photodynamic therapy where Bcl-2 is among the PDT targets, and discuss the implications of the results.