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Antitumor effect of a short peptide on p53-null SKOV3 ovarian cancer cells
- Source :
- Anti-Cancer Drugs. 30:973-982
- Publication Year :
- 2019
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2019.
-
Abstract
- Fibroblast growth factor-2 (FGF2) is a protein ligand, which exerts essential roles in development, angiogenesis, and tumor progression via activation of the downstream signaling cascades. Accumulating evidence has demonstrated that FGF2 is involved in the progression of ovarian cancer, providing a novel potential target for ovarian cancer therapy. In this study, we showed that FGF2 is significantly increased in ovarian tumors, and is negatively associated with the overall survival of ovarian cancer by database analysis. A short peptide obtained from a heptapeptide phage display library suppressed FGF2-induced proliferation, migration, and invasion of the p53-null epithelial ovarian cancer (EOC) cells. Further investigations revealed that the short peptide antagonized the effects of FGF2 on G0/G1 to S cell phase promotion, cyclin D1 expression, and MAPK and Akt signaling activation, which might contribute to the mechanism underlying the inhibitory effects of the short peptide on the aggressive phenotype of the ovarian cancer cells triggered by FGF2. Moreover, the short peptide might have the potentials of reversing FGF2-induced resistance to the doxorubicin via downregulation of the antiapoptotic proteins and counteracting of the antiapoptotic effects of FGF2 on p53-null EOC cells. Taken together, the short peptide targeting FGF2 may provide a novel strategy for improving the therapeutic efficiency in a subset of EOC.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Cancer Research
endocrine system diseases
Angiogenesis
Antineoplastic Agents
Apoptosis
Kaplan-Meier Estimate
Carcinoma, Ovarian Epithelial
S Phase
03 medical and health sciences
0302 clinical medicine
Cyclin D1
Downregulation and upregulation
Peptide Library
Cell Line, Tumor
medicine
Humans
Pharmacology (medical)
Peptide library
Protein kinase B
Cell Proliferation
Ovarian Neoplasms
Pharmacology
integumentary system
Chemistry
medicine.disease
female genital diseases and pregnancy complications
030104 developmental biology
Oncology
Doxorubicin
Drug Resistance, Neoplasm
Tumor progression
030220 oncology & carcinogenesis
embryonic structures
Cancer research
Female
Fibroblast Growth Factor 2
Tumor Suppressor Protein p53
Peptides
Ovarian cancer
Subjects
Details
- ISSN :
- 09594973
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Anti-Cancer Drugs
- Accession number :
- edsair.doi.dedup.....d8f50ef98147bbf69d7d7d0979960d06