Combined effect of 5-fluorouracil and recombinant tumor necrosis factor against human gastric carcinoma cell lines.
This study was performed to investigate the direct effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interleukin-2 (rH-IL-2), either alone or in combination, on the cytotoxicity of 5-FU measured by MTT assay against human gastric adenocarcinoma cell lines (MKN-28 and MKN-45), and also to determine the optimal schedule for their combination. The antitumor activity of rH-TNF was enhanced more than 42% by 10(2) U/ml of rH-IL-2. The enhancing effects of rH-TNF and rH-IL-2 on the cytotoxicity of 5-FU were evaluated in terms of Modification Index(MI), the MI value at 10 U/ml rH-TNF was 1.6; the MI at the same concentration of rH-TNF in the presence of 10(2) U/ml of rH-IL-2 was 2.1. These results demonstrated that the antitumor effect of 5-FU was enhanced 1.6 times by 10 U/ml of rH-TNF and further enhanced by the combined use of rH-TNF and rH-IL-2. The combined effect of equal concentrations of 5-FU and rH-TNF was superior or equivalent to that of 5-FU or rH-TNF alone. The sequence of 5-FU followed by rH-TNF and rH-IL-2 showed a higher inhibitory effect than the reverse sequence. This sequence combination seems worthy of further consideration for the treatment of gastric cancer.
Li
Y
Y
First Affiliated Hospital, Zhejiang Medical School, China.
Ito
S
S
Cheng
W
W
Ishii
Y
Y
D000230:Adenocarcinoma; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005472:Fluorouracil / Q000633:toxicity*; D006801:Humans; D007376:Interleukin-2 / Q000633:toxicity*; D007700:Kinetics; D011994:Recombinant Proteins / Q000633:toxicity; D013274:Stomach Neoplasms; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D014410:Tumor Stem Cell Assay
D000964:Antimetabolites, Antineoplastic; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005472:Fluorouracil