• 2022-09
  • 2022-08
  • 2022-07
  • 2022-05
  • 2022-04
  • 2021-03
  • 2020-08
  • 2020-07
  • 2020-03
  • 2019-11
  • 2019-10
  • 2019-09
  • 2019-08
  • 2019-07
  • br Previous studies indicated that


    Previous studies indicated that apatinib could inhibit metastasis and tumorigenesis in patients with TNBC [3,22,23]. In this study, apatinib enhanced the pro-apoptotic, anti-migratory and anti-invasive effects of cisplatin on MDA-MB-231 cells. In addition, apatinib is an anti-angio-genic drug and a small-molecule inhibitor of VEGFR2, which could markedly inhibit VEGF signaling pathway [24,25]. Moreover, apatinib induced cell apoptosis and inhibited cell proliferation via blocking VEGF pathway [26,27]. Prior study also demonstrated that apatinib induce apoptosis in intrahepatic cholangiocarcinoma via inhibiting VEGF signaling [27]. Thus, we hypothesized that apatinib enhance the pro-apoptotic, anti-migratory and anti-invasive effects of cisplatin in TNBC through VEGFR2 signaling. Our results indicated that cisplatin has no effect on the 2-NBDG of p-VEGFR2, while combination cis-platin with apatinib significantly decreased the expressions of p-VEGFR2. Therefore, we supposed that apatinib could enhance the anti-tumor effect of cisplatin via VEGFR2. Whether other factors are in-volved in this process needs to be clarified.
    Angiogenesis and PI3K/Akt/mTOR pathway are the major mole-cular targets for the treatment of breast cancer [28]. Hong et al illu-strated that VEGF activated VEGFR2 and initiated a PI3K-AKT-mTOR pathway, which exhibited an anti-apoptotic effect [27]. Inhibition of angiogenesis through the blocking of the VEGFR2-Akt-mTOR signaling pathway has exerted as a potential method in anti-tumor therapy [29,30]. In this study, we also found that cisplatin decreased the ex-pressions of p-Akt and p-mTOR, while the levels of these proteins were further reduced in the presence of apatinib. Therefore, the possible mechanism was that apatinib decreased the VEGF-mediated Akt/mTOR signaling activity. Thus, we infer that intracellular VEGFR2 inhibitors, apatinib, 2-NBDG could enhance the anti-tumor effect of cisplatin via VEGFR2-Akt-mTOR signaling pathway.
    5. Conclusion
    In conclusion, apatinib enhanced the anti-tumor effects of cisplatin on MDA-MB-231 cells via inhibition of VEGFR2. The results suggested that the combination of apatinib with cisplatin may serve as a potential method in the treatment of patients with TNBC.
    Conflict of interest
    The present study was supported by a grant from Clinical research of general medicine of China (grant no. 2016QK013). The authors thank Dr liuhao (Bengbu Medical College) for his helpful discussions.
    [26] M. Huang, B. Huang, G. Li, S. Zeng, Apatinib affect VEGF-mediated cell prolifera-tion, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT
    [30] M. Ducreux, P. Osterlund, J.P. Pignon, Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer-A definite conclusion? Semin. Oncol. 44
    Contents lists available at ScienceDirect
    Gynecologic Oncology
    Apatinib exerts anti-tumour effects on ovarian cancer cells
    a Department of Gynecology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China
    b Beijing Center for Physical and Chemical Analysis, No. 7 Fengxianzhong Road, Haidian District, Beijing 100094, China
    • Apatinib does not appreciably affect the proliferation and vitality of ovarian cancer cells.
    • Apatinib inhibits ovarian cancer cells migration.
    • Apatinib suppresses the epithelial-mesenchymal transition (EMT).
    • Apatinib inhibits the JAK/STAT3, PI3K/Akt and Notch signalling pathways.
    • Apatinib inhibits tumour growth in vivo.
    Article history:
    Ovarian cancer