|Table of Contents|

Effect and mechanism of ginkgetin on cisplatin resistance of anaplastic thyroid cancer cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 14
Page:
2570-2575
Research Field:
Publishing date:

Info

Title:
Effect and mechanism of ginkgetin on cisplatin resistance of anaplastic thyroid cancer cells
Author(s):
LI Xianbin1WANG Xiaodong2LI Chunyan3LI Chunxiang2
1.Clinical Laboratory;2.Department of Nuclear Medicine;3.Department of Ultrasonography,the First Affiliated Hospital of Qiqihar Medical College,Heilongjiang Qiqihar 161041,China.
Keywords:
ginkgetinAMPK/mTOR signaling pathwayanaplastic thyroid cancercisplatin resistance
PACS:
R736.1
DOI:
10.3969/j.issn.1672-4992.2023.14.002
Abstract:
Objective:To investigate the effect and molecular mechanism of ginkgetin on cisplatin (DDP) resistance in anaplastic thyroid cancer (ATC) cells.Methods:Human ATC cells 8505C were cultured in vitro and 8505C DDP resistant cell lines (8505C/DDP) were constructed and treated with DDP (1.25,2.5,5,10,20 μg/mL) or ginkgetin (1.25,2.5,5,10,20 μmol/L).CCK-8 assay was used to detect the toxicity of DDP and ginkgetin on 8505C and 8505C/DDP cells and the toxicity of the combination of DDP and ginkgetin on 8505C/DDP cells.The 8505C/DDP cells were separated into DDP group,DDP+ginkgetin group,DDP+AMPK inhibitor group,and DDP+ginkgetin+AMPK inhibitor group.CCK-8 assay was applied to detect cell proliferative viability.Annexin V-FITC/PI double staining was applied to detect cell apoptosis.Scratch-healing assay was applied to examine cell migration ability.Transwell assay was used to detect cell invasiveness.Western Blot was applied to detect expression of proteins related to AMPK/mTOR signaling pathway.Results:The IC50 of DDP on 8505C/DDP cells was higher than that in 8505C cells (P<0.05).There was no obvious difference in IC50 of ginkgetin on 8505C/DDP and 8505C cells (P>0.05).Ginkgetin could enhance the sensitivity of DDP to 8505C/DDP cells (P<0.05).Compared with 8505C cells,the p-AMPK/AMPK ratio in 8505C/DDP cells was decreased,while the p-mTOR/mTOR ratio was increased (P<0.05).Ginkgetin could increase p-AMPK/AMPK ratio and decrease p-mTOR/mTOR ratio in 8505C cells and 8505C/DDP cells (P<0.05).Compared with DDP group,the proliferation activity,scratch healing rate,invasion number and p-mTOR/mTOR ratio of 8505C/DDP cells in DDP+ginkgetin group were decreased,while the apoptosis rate and p-AMPK/AMPK ratio were increased (P<0.05).Compared with DDP+ginkgetin group,cell proliferation activity,scratch healing rate,invasion number and p-mTOR/mTOR ratio were increased in DDP+ginkgetin+AMPK inhibitor group,while apoptosis rate and p-AMPK/AMPK ratio were decreased (P<0.05).Conclusion:Ginkgetin can reduce the resistance of 8505C/DDP cells to DDP,and enhance the inhibition of DDP on proliferation,migration and invasion of 8505C/DDP cells,as well as the induction of apoptosis,and the mechanism of action may be related to the activation of AMPK/mTOR signaling pathway.

References:

[1]MANIAKAS A,ZAFEREO M,CABANILLAS ME.Anaplastic thyroid cancer:New horizons and challenges[J].Endocrinol Metab Clin North Am,2022,51(2):391-401.
[2]ALLEGRI L,DOMENIS R,NAVARRA M,et al.Dihydrotanshinone exerts antitumor effects and improves the effects of cisplatin in anaplastic thyroid cancer cells[J].Oncol Rep,2021,46(3):204.
[3]LEE YJ,KANG YR,LEE SY,et al.Ginkgetin induces G2-phase arrest in HCT116 colon cancer cells through the modulation of b-Myb and miRNA34a expression[J].Int J Oncol,2017,51(4):1331-1342.
[4]CAO J,TONG C,LIU Y,et al.Ginkgetin inhibits growth of breast carcinoma via regulating MAPKs pathway[J].Biomed Pharmacother,2017,96:450-458.
[5]LIU Q,CHEN L,YIN W,et al.Anti-tumor effect of ginkgetin on human hepatocellular carcinoma cell lines by inducing cell cycle arrest and promoting cell apoptosis[J].Cell Cycle,2022,21(1):74-85.
[6]CHENG J,LI Y,KONG J.Ginkgetin inhibits proliferation of HeLa cells via activation of p38/NF-κB pathway[J].Cell Mol Biol (Noisy-le-grand),2019,65(4):79-82.
[7]LOU JS,ZHAO LP,HUANG ZH,et al.Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer[J].Phytomedicine,2021,80:153370.
[8]LI Y,SUN Q,CHEN S,et al.Monensin inhibits anaplastic thyroid cancer via disrupting mitochondrial respiration and AMPK/mTOR signaling[J].Anticancer Agents Med Chem,2022,22(14):2539-2547.
[9]LV C,YANG H,YU J,et al.ABCA8 inhibits breast cancer cell proliferation by regulating the AMP activated protein kinase/mammalian target of rapamycin signaling pathway[J].Environ Toxicol,2022,37(6):1423-1431.
[10]杨丰侨,柏磊,盛玉清,等.银杏双黄酮介导AMPK/COX-2通路对黑色素瘤细胞凋亡的影响[J].广西医科大学学报,2022,39(1):81-86. YANG FQ,BAI L,SHENG YQ,et al.Effect of ginkgo biloba biflavones on apoptosis of melanoma cells by mediating AMPK/COX-2 pathway[J].Journal of Guangxi Medical University,2022,39(1):81-86.
[11]WEI L,JIAN P,ERJIONG H,et al.Ginkgetin alleviates high glucose-evoked mesangial cell oxidative stress injury,inflammation,and extracellular matrix (ECM) deposition in an AMPK/mTOR-mediated autophagy axis[J].Chem Biol Drug Des,2021,98(4):620-630.
[12]TRAN T,CYPEN S,DEL VALLE ESTOPINAL M,et al.Anaplastic thyroid carcinoma with ocular then orbital metastases[J].Case Rep Ophthalmol,2022,13(1):76-81.
[13]HU Y,ZHOU N,WANG R.Apatinib strengthens the anti-tumor effect of cisplatin in thyroid carcinoma through downregulating VEGFR2[J].J Buon,2021,26(2):613-619.
[14]OZDEMIR KUTBAY N,BIRAY AVCI C,SARER YUREKLI B,et al.Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells[J].J Biochem Mol Toxicol,2020,34(10):e22547.
[15]WANG Z,ZHU Z,LI C,et al.NMIIA promotes tumorigenesis and prevents chemosensitivity in colorectal cancer by activating AMPK/mTOR pathway[J].Exp Cell Res,2021,398(1):112387.
[16]GUO L,CUI J,WANG H,et al.Metformin enhances anti-cancer effects of cisplatin in meningioma through AMPK-mTOR signaling pathways[J].Mol Ther Oncolytics,2020,20:119-131.

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黑龙江省卫生健康委科研计划(编号:20210909040360)
Last Update: 1900-01-01