Objective： To investigate the role of apatinib in promoting autophagy and apoptosis of endothelial cells through the vascular endothelial growth factor receptor（VEGFR）pathway and its potential mechanism. Methods： Human umbilical vein endothelial Cells（HUVEC）was incubate with different concentrations of apatinib for 48 h to detect cell viability,apoptosis and autophagy levels;the level of reactive oxygen species （ROS）generation was detected by the ROS detection kit ;the expression levels of phosphorylated VEGFR-2,phosphorylated mammalian target of rapamycin（mTOR）,mTOR,phosphorylated Akt,and Akt were detected by Western blot. Results： Apatinib promoted cell autophagy and apoptosis,and reduces cell viability. The optimal concentration of apatinib was 40mol·L-1（increasing the apoptotic rate from 1.31%±0.08% to 22.43%±2.90%, and cell viability from 100.03%±8.20% down to 11.42%±1.08 %）;at the same time,apatinib significantly reduced the expression of phosphorylated VEGFR-2,phosphorylated Akt and phosphorylated mTOR. Conclusion： Apatinib promotes autophagy and apoptosis of endothelial cells through VEGFR pathway.
FANG Chun, HE Dan-shuang, KANG Bao-guo, WANG Li-fang, TAO Ling
. Study on the Relationship between autophagy and apoptosis of vascular endothelial cells promoted by apatinib through VEGFR pathway*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(5)
: 832
-838
.
DOI: 10.16155/j.0254-1793.2021.05.10
[1] SEVELDA F, MAYR L, KUBISTA B, et al.EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance[J].J Exp Clin Cancer Res, 2015, 34(1):134
[2] LI J, YANG Z, LI Y, et al.Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment[J].Oncotarget, 2016, 7(28):172
[3] ANDO K, HEYMANN MF, STRESING V, et al.Current therapeutic strategies and novel approaches in osteosarcoma[J].Cancers, 2013, 5(2):591
[4] WIERSTRA I.FOXM1(Forkhead box M1)in tumorigenesis: overexpression in human;cancer, implication in tumorigenesis[J].Adv Cancer Res, 2013, 11(9):191
[5] PENG H, ZHANG Q, LI J, et al.Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma[J].Oncotarget, 2016, 7(13):17220
[6] HU X, CAO J, HU W, et al.Multicenter phase Ⅱ study of apatinib in non-triple-negative metastatic breast cancer[J].BMC Cancer, 2014, 14(1):820
[7] LI J, QIN S, XU J, et al.Randomized, double-blind, placebo-controlled phase iii trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction[J].J Clin Oncol, 2016, 2(15):2063
[8] PENG QX, HAN YW, ZHANG YL, et al.Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma[J].Oncotarget, 2017, 8(32):52813
[9] LI F, LIAO Z, ZHAO J, et al.Efficacy and safety of apatinib in stage Ⅳ sarcomas:experience of a major sarcoma center in China[J].Oncotarget, 2015, 8(38):64471
[10] DENG XS, WANG S, DENG A, et al.Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers[J].Cell Cycle, 2012, 11(2):367
[11] TANG Q, LI G, WEI X, et al.Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma[J].Cancer Letters, 2013, 336(2):325
[12] JAKHAR R, PAUL S, BHARDWAJ M, et al.Astemizole istamine induces beclin-1-independent autophagy by targeting p53-dependent crosstalk between autophagy and apoptosis[J].Cancer Lett, 2016, 372(1):89
[13] SHI WY, XIAO D, WANG L, et al.Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy[J].Cell Death Dis, 2012, 3(3):275
[14] LOHELA M, BRY M, TAMMELA T, et al.VEGFs and receptors involved in angiogenesis versus lymphangiogenesis[J].Curr Opin Cell Biol, 2009, 21(2):154
[15] YUE J, GANG W, QI X, et al.Antiangiogenic effects of AA-PMe on HUVECs in vitro and zebrafish in vivo[J].Oncotargets & Therapy, 2018, 11(3):1871
[16] SARABIPOUR S, BALLMER-HOFER K, HRISTOVA K.VEGFR-2 conformational switch in response to ligand binding[J].Life Sci, 2016, 5(13):876
