Back
Full-text
Journal article

Effect of RasGAP N2 fragment-derived peptide on tumor growth in mice.

Show more…
  • 2009-05-28
Published in:
  • Journal of the National Cancer Institute. - 2009
Amino Acid Sequence
Animals
Antineoplastic Agents
Apoptosis
Cisplatin
Colonic Neoplasms
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Drug Synergism
GTPase-Activating Proteins
HCT116 Cells
Humans
Infusions, Parenteral
Mice
Mice, Nude
Molecular Sequence Data
Mutagens
Peptide Fragments
Transplantation, Heterologous
English Peptides that interfere with the natural resistance of cancer cells to genotoxin-induced apoptosis may improve the efficacy of anticancer regimens. We have previously reported that a cell-permeable RasGAP-derived peptide (TAT-RasGAP(317-326)) specifically sensitizes tumor cells to genotoxin-induced apoptosis in vitro. Here, we examined the in vivo stability of a protease-resistant D-form of the peptide, RI.TAT-RasGAP(317-326), and its effect on tumor growth in nude mice bearing subcutaneous human colon cancer HCT116 xenograft tumors. After intraperitoneal injection, RI.TAT-RasGAP(317-326) persisted in the blood of nude mice for more than 1 hour and was detectable in various tissues and subcutaneous tumors. Tumor-bearing mice treated daily for 7 days with RI.TAT-RasGAP(317-326) (1.65 mg/kg body weight) and cisplatin (0.5 mg/kg body weight) or doxorubicin (0.25 mg/kg body weight) displayed reduced tumor growth compared with those treated with either genotoxin alone (n = 5-7 mice per group; P = .004 and P = .005, respectively; repeated measures analysis of variance [ANOVA, two-sided]). This ability of the RI.TAT-RasGAP(317-326) peptide to enhance the tumor growth inhibitory effect of cisplatin was still observed at peptide doses that were at least 150-fold lower than the dose lethal to 50% of mice. These findings provide the proof of principle that RI.TAT-RasGAP(317-326) may be useful for improving the efficacy of chemotherapy in patients.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/248182
Statistics
Document views: 11 File downloads:
  • fulltext.pdf: 0