Antisense bcl-2 retrovirus vector increases the sensitivity of a human gastric adenocarcinoma cell line to photodynamic therapy

The bcl-2 oncoprotein directly prolongs cellular survival by blocking apopt osis and its overexpression is associated with cellular resistance to killi ng by chemotherapeutic drugs and gamma-irradiation. Meanwhile, it has been shown that bcl-2 antisense oligonucleotide can induce apoptosis or increase toxicity of the treatment in tumors irt vivo and in vitro, However, it is difficult to obtain stable transfection by this approach and there are no r eports about the effect of an antisense bcl-2 on the sensitivity to oxidati ve stress induced by photodynamic therapy (PDT), Here we investigated the e ffect of an antisense bcl-2 RNA retrovirus vector transfer on the sensitivi ty of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitizati on in a human gastric adenocarcinoma MGC803 cell line. The results indicate that antisense bcl-2-infected MGC803 cells expressed exogenous antisense b cl-2 mRNA measured by reverse transcription polymerase chain reaction and s ignificantly reduced bcl-2 protein determined by western blotting analysis. The decreased expression of bcl-2 protein was accompanied by increased pho totoxicity and susceptibility to apoptosis induced by 2-BA-2-DMHA PDT. Our finding suggests that reduction of bcl-2 protein in gastric cancers, and po ssibly also in a variety of other tumors, may be a novel and rational appro ach to improve photosensitivity and the treatment outcome.