['Vasoactive intestinal peptide (VIP) is one of several small neuropeptides that affect cancer growth. A lipophilic VIP analog, stearyl-Nle(17)-neuroten-sin(6-11)VIP(7-28) (SNH) that inhibited lung carcinoma growth has been described previously. The experiments performed were clonogenic assays in vitro and tumor xenografts in nude mice in vivo. These studies were now extended to colon carcinoma and to combination therapy with chemotherapeutic agents.', 'Assays were performed with cell lines, and tumor proliferation was assessed using the (3-[4,5-dimethylthiazol-2-yl-5]-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H tetrazolium) (MTS) colorimetric assay for mitochondrial function of living cells.', 'The lipophilic analog (SNH) enhanced the antiproliferative activity of diverse chemotherapeutic agents: doxorubicine (antibiotic); vinorelbine (vinca alkaloid, antimicrotubule formation); paclitaxel (antimicrotubule agent); gemcitabine (antimetabolite); irinotecan (topoisomerase I inhibitor); and cisplatin (platinum compound acting as an alkylating agent). In all cases, the antiproliferative effect of SNH and the chemotheraputic agent was at least additive and for some combinations and concentrations even synergistic. For example, 2 microM of the antagonist that produced a 15-20% growth inhibition in the nonsmall cell lung carcinoma cell line reduced the IC(50) by 2-4-fold for most of the chemotherapeutic agents tested. Higher analog concentrations were even more efficacious. Similar results were obtained with colon carcinoma cell lines.'] Does a lipophilic vasoactive intestinal peptide analog enhance the antiproliferative effect of chemotherapeutic agents on cancer cell lines?