Antitumor effect of a short peptide on p53-null SKOV3 ovarian cancer cells
Antitumor effect of a short peptide on p53-null SKOV3 ovarian cancer cells
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短肽对 p53 缺失 SKOV3 卵巢癌细胞的抗肿瘤作用
DOI：
10.1097/cad.0000000000000830
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发表时间：
2019-11-01
影响因子：
2.3
通讯作者：
Wu, Xiao-ping
中科院分区：
文献类型：
--
作者：
Huang, Yi-shan;Wang, Tian-xiang;Wu, Xiao-ping
成纤维细胞生长因子-2 （FGF2）是一种蛋白质配体，通过激活下游信号级联反应在发育、血管生成和肿瘤进展中发挥重要作用。越来越多的证据表明，FGF2参与卵巢癌的进展，为卵巢癌治疗提供了新的潜在靶点。在本研究中，我们通过数据库分析发现FGF2在卵巢肿瘤中显著升高，并与卵巢癌的总生存率呈负相关。从七肽噬菌体展示文库中获得的短肽抑制了fgf2诱导的p53-null上皮性卵巢癌（EOC）细胞的增殖、迁移和侵袭。进一步研究发现，短肽可拮抗FGF2对G0/G1至S细胞期促进、cyclin D1表达、MAPK和Akt信号激活的作用，这可能是短肽抑制FGF2引发的卵巢癌细胞侵袭性表型的机制之一。此外，短肽可能通过下调抗凋亡蛋白和抵消FGF2对p53缺失的EOC细胞的抗凋亡作用，逆转FGF2诱导的对阿霉素的抗性。综上所述，靶向FGF2的短肽可能为提高EOC亚群的治疗效率提供了一种新的策略。
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.