OBJECTIVE: To study the inhibitory effect induced by combined treatment of TNF alpha and antisense oligodeoxynucleotide on the growth of human pancreatic adenocarcinoma cell line (PC-2) cells. METHOD: TNF alpha and synthesized antisense c-myc or Ki-ras phosphorothioate oligodeoxynucleotide (ASPODN) were added to the culture media of PC-2 cells, whereas the groups treated with TNF alpha or ASPODN alone were used as controls. The cell growth rate was estimated by cell count and MTT analysis, the endogenous target gene expression was studied by adopting RT-PCR-Southern blot technique, and cell apoptosis was detected in situ. RESULTS: The cell growth was inhibited much more obviously in the groups of combined treatment than in the groups treated with TNF alpha or ASPODN alone. Marked inhibition of endogenous Ki-ras and c-myc expression was observed in the groups treated with Ki-ras and c-myc ASPODN. The amounts of apoptotic cells were 8.0% and 8.4% in the groups of TNF alpha + Ki-ras ASPODN and TNF alpha + c-myc ASPODN, and were 5.2%, 4.8% and 5.4% for TNF alpha, Ki-ras ASPODN and c-myc ASPODN respectively. CONCLUSION: Our results demonstrate that the inhibitory effect induced by combined treatment of TNF alpha and ASPODN on cell growth was stronger than that induced by TNF alpha or ASPODN alone.