Bcl-2 antisense oligonucleotides chemosensitize human gastric cancer in a SCID mouse xenotransplantation model

We used Bcl-2 antisense oligonucleotides (G3139) to chemosensitize human ga stric cancer by downregulation of Bcl-2 expression in vivo. Oligonucleotide s and cisplatin were administered systemically in a human gastric cancer SC ID mouse model, and Bcl-2 expression, apoptosis, tumor size, and survival w ere assessed. Used alone, G3139 treatment led to downregulation of Bcl-2 an d moderate tumor reduction compared to saline control. G3139 combined with cisplatin treatment markedly enhanced the antitumor effect of cisplatin (70 % tumor size reduction vs. cisplatin alone), associated with increased apop tosis measured in tumor biopsy specimens. Combined treatment with G3139 and cisplatin prolonged survival of the tumor-bearing SCID mice by more than 5 0% without adding significant drug-related toxicity. Treatment with Bcl-2 a ntisense oligonucleotides is thus a promising novel approach to enhance ant itumor activity of cisplatin or other drugs used in gastric cancer therapy and warrants further evaluation in clinical trials.