In vitro growth suppression of human glioma cells by a 16-mer oligopeptide: a potential new treatment modality for malignant glioma.
Fibroblast growth factor-2 (FGF-2) is involved as an autocrine growth factor in the autonomous proliferation of glioma cells. To develop a new strategy for treating patients with glioma, we studied the effect on human glioma cells of a 16-mer oligopeptide with conformational similarity to the putative receptor-binding domain of FGF-2. A synthesized oligonucleotide was assessed its receptor-binding activity by BIAcore instrument. Its biological effect on glioma cell lines was examined in vitro by MTT assay. The peptide suppressed the in vitro growth of human glioma cells U87MG, T98G and U251MG cells, but not of A431 cells whose growth is not dependent on FGF-2. Apoptotic bodies were noted after 24-h incubation in the presence of the peptide; Ac-YVAD-CHO, a caspase-3 inhibitor, suppressed apoptosis. Furthermore, we examined the modulation of the cytotoxic effect of anticancer drugs by the oligopeptide. The addition of this oligopeptide to the chemotherapeutic agents CDDP, ACNU and VP16 had additive effects in vitro. These results suggest that the pathway of the FGF-2 autocrine loop through the FGF receptor plays an important role in the proliferation of glioma cells. New drugs targeting this loop may be highly effective in treating FGF-2-dependent tumors. Our results suggest that its addition to the therapeutic arsenal may lead to improved treatment regimens for patients with FGF-2-dependent tumors.
Kono
Katsuhiko
K
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Sakyoku, Kyoto, Japan.
Ueba
Tetsuya
T
Takahashi
Jun A
JA
Murai
Nozomu
N
Hashimoto
Nobuo
N
Myoumoto
Akira
A
Itoh
Nobuo
N
Fukumoto
Manabu
M
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D004357:Drug Synergism; D005047:Etoposide / Q000627:therapeutic use; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D015376:Nimustine / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use*; D016372:RNA, Antisense / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009842:Oligopeptides; D016372:RNA, Antisense; D015376:Nimustine; D016222:Fibroblast Growth Factor 2; D005047:Etoposide; D002945:Cisplatin