Therapeutic Potential of Antisense Bcl-2 as a Chemosensitizer for Patients with Gastric Carcinoma

摘要

We performed a preclinical evaluation of antisense (AS) Bcl-2 as an enhancer of the chemotherapeutic effect in the treatment of gastric carcinoma. Antisense Bcl-2 was used with 18-mer phosphorothiated oligonucleotides for MKN-45 gastric carcinoma cell line. Drug sensitivity in vitro was evaluated by the MTT assay, and antitumor effect in vivo was evaluated by the nude mouse xenograft. Drug sensitivity to doxorubicin, cisplatin, and paclitaxel was increased to 3-4-fold when used in combination with AS Bcl-2, which was determined with IC_(50) values. Increased drug sensitivity was associated with apoptotic cell death, which was activated by Bax, caspase-3, and Poly (ADP-ribose) polymerase (PARP). The antitumor effect of CDDP and TXL in vivo was significantly enhanced in combination with AS Bcl-2. Combination treatment with AS Bcl-2 and anticancer drugs, which is targeting Bcl-2, may be a new strategy for enhancing of the chemotherapeutic effect in the treatment of gastric carcinoma.