|Table of Contents|

Inhibitory effects of a novel polyoxometalate compound {BiW8O30} on glioblastoma cells in vivo and in vitro

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

Issue:
2024 05
Page:
811-818
Research Field:
Publishing date:

Info

Title:
Inhibitory effects of a novel polyoxometalate compound {BiW8O30} on glioblastoma cells in vivo and in vitro
Author(s):
JIA Di1; ZHU Xinping2; YANG Chao1; ZHANG Chunjing1; LI Shuyan1; ZHAO Zhenglin1; GAO Han1; SHI Yan1; ZHAO Weiming2
1.Qiqihar Medical University,Medical Technology Department,Heilongjiang Qiqihar 161006,China;2.Heilongjiang University of Chinese Medicine,Heilongjiang Harbin 150040,China.
Keywords:
{BiW8O30}; glioblastoma; proliferation; migration; invasion; apoptosis
PACS:
R739.41
DOI:
10.3969/j.issn.1672-4992.2024.05.005
Abstract:
Objective:To investigate the inhibitory effect of a novel polyoxometalate compound {BiW8O30} on glioblastoma LN229 and U251 cells in vivo and in vitro,and the possible mechanism.Methods:LN229 and U251 cells were treated with different concentrations of {BiW8O30}.CCK-8 assay was used to detect cell proliferation.Cell scratch and invasion assay to detect cell migration and invasion.Cell apoptosis was detected by flow cytometry.Nuclear morphological changes were observed by DAPI staining.The proliferation ability of tumor in vivo was detected by subcutaneous transplantation of tumor model in nude mice.Western blot was used to detect the expression level of apoptosis-related proteins in cells.Proteomic sequencing was used to analyze thepossible mechanisms of inhibitory effect of {BiW8O30} on glioblastoma cells.Results:Compared with the control group,the cell survival rate,scratch healing rate and invasive cell number of {BiW8O30} treatment group were significantly decreased(P＜0.001).The apoptosis rate of the {BiW8O30} treatment group was significantly higher than that of the control group(P＜0.05).DAPI staining results showed that some cells in the {BiW8O30} group showed morphological changes such as nuclear condensation and nuclear fragmentation.{BiW8O30} inhibited the growth of LN229 xenografts in nude mice compared with control group(P＜0.05).Western blot results showed that compared with the control group,the expression of apoptosis-related protein XIAP was decreased and caspase 3 was increased in the {BiW8O30} group(P＜0.05).Proteome sequencing analysis showed that a total of 559 proteins were significantly differentially expressed before and after {BiW8O30} treatment,of which 250 proteins were up-regulated and 309 proteins were down-regulated(consistent with adj.P-value<0.05,|Fold change|>1.5).Through GO and KEGG enrichment analysis,it was found that differential proteins were enriched in pathways such as regulation of programmed cell death,apoptotic process,regulation of cell motility,cell adhesion.Conclusion:{BiW8O30} inhibits the proliferation in vivo and in vitro,migration and invasion of glioblastoma cells,and induces cell apoptosis.The possible mechanisms may be related to pathways of apoptosis process,cell adhesion and motility.

References:

[1]LOUIS DN,PERRY A,WESSELING P,et al.The 2021 WHO classification of tumors of the central nervous system:a summary［J］.Neuro Oncol,2021,23(8):1231-1251.
[2] HORBINSKI C,NABORS LB,PORTNOW J,et al.NCCN Guidelines Insights:Central nervous system cancers,version 2.2022［J］.J Natl Compr Canc Netw,2023,21(1):12-20.
[3] OSTROM QT,PRICE M,NEFF C,et al.CBTRUS statistical report:Primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019［J］.Neuro Oncol,2022,24(Suppl 5):v1-v95.
[4] LAPOINTE S,PERRY A,BUTOWSKI NA.Primary brain tumours in adults［J］.Lancet,2018,392(10145):432-446.
[5] TAN AC,ASHLEY DM,LOPEZ GY,et al.Management of glioblastoma:State of the art and future directions［J］.CA Cancer J Clin,2020,70(4):299-312.
[6] KAYNAK A,DAVIS HW,VALLABHAPURAPU SD,et al.SapC-DOPS as a novel therapeutic and diagnostic agent for glioblastoma therapy and detection:Alternative to old drugs and agents［J］.Pharmaceuticals(Basel),2021,14(11):1193.
[7] FURNARI FB,CLOUGHESY TF,CAVENEE WK,et al.Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma［J］.Nat Rev Cancer,2015,15(5):302-310.
[8] CHANDRAN M,CANDOLFI M,SHAH D,et al.Single vs.combination immunotherapeutic strategies for glioma［J］.Expert Opin Biol Ther,2017,17(5):543-554.
[9] BHUJBAL SV,DE VOS P,NICLOU SP.Drug and cell encapsulation:alternative delivery options for the treatment of malignant brain tumors［J］.Adv Drug Deliv Rev,2014,67-68:142-153.
[10] CHEREVAN AS,NANDAN SP,ROGER I,et al.Polyoxometalates on functional substrates:Concepts,synergies,and future perspectives［J］.Adv Sci(Weinh),2020,7(8):1903511.
[11] COLOVIC MB,LACKOVICM,LALATOVIC J,et al.Polyoxometalates in biomedicine:Update and overview［J］.Curr Med Chem,2020,27(3):362-379.
[12] LI XH,CHEN WL,LI YG,et al.Multifunctional rare earth-containing polyoxometalates achieving high-efficiency tumor therapy and visual fluorescence monitoring［J］.Inorganic Chemistry Communications,2019,104(6):40-47.
[13] BIJELIC A,AURELIANO M,ROMPEL A.Polyoxometalates as potential next-generation metallodrugs in the combat against cancer［J］.Angew Chem Int Ed Engl,2019,58(10):2980-2999.
[14] JIA D,GONG L,LI Y,et al.{BiW8O30} exerts antitumor effect by triggering pyroptosis and upregulating reactive oxygen species［J］.Angew Chem Int Ed Engl,2021,60(39):21449-21456.
[15]祝欣萍,贾迪,林少辉,等.新型多金属氧酸盐药物{BiW8O30}对肝癌SK-HEP-1细胞的抑制作用［J］.癌变·畸变·突变,2022,34(01):47-52,66. ZHU XP,JIA D,LIN SH,et al.Inhibitory effects of a novelpolyoxometalate drug {BiW8O30}on liver cancer SK-HEP-1 cells［J］.Carcinogenesis，Teratogenesis & Mutagenesis,2022,34(01):47-52,66.
[16] OBEXER P,AUSSERLECHNER MJ.X-linked inhibitor of apoptosis protein-a critical death resistance regulator and therapeutic target for personalized cancer therapy［J］.Front Oncol,2014,4:197.
[17] AFROZE N,PRAMODH S,SHAFARIN J,et al.Fisetin deters cell proliferation,induces apoptosis,alleviates oxidative stress and inflammation in human cancer cells,HeLa［J］.Int J Mol Sci,2022,23(3):1707.
[18] LU KW,LU TJ,CHUEH FS,et al.Allyl isothiocyanate(AITC) induces apoptotic cell death in vitro and exhibits anti-tumor activity in a human glioblastoma GBM8401/luc2 model［J］.Int J Mol Sci,2022,23(18):10411.
[19] ZHANG ZM,DUAN X,YAO S,et al.Cation-mediated optical resolution and anticancer activity of chiral polyoxometalates built from entirely achiral building blocks［J］.Chem Sci,2016,7(7):4220-4229.
[20] YAN HF,ZOU T,TUO QZ,et al.Ferroptosis:mechanisms and links with diseases［J］.Signal Transduct Target Ther,2021,6(1):49.
[21] 庞敬瑶，李佩玲，Beilerli Aferin，等.基于铁死亡的癌症治疗新策略［J］.现代肿瘤医学，2021,29(06)：1058-1061. PANG JY,LI PL,BEILERLI AFERIN,et al.New strategies of cancer therapy based on ferroptosi［J］.Modern Oncology，2021,29(06)：1058-1061.

Memo

Memo:
黑龙江省齐齐哈尔市科技计划联合引导项目(编号：LHYD-202001);黑龙江省省属高等学校基本科研业务费科研项目（编号：2019-KYYWF-1255）;黑龙江省普通本科高等学校青年创新人才培养计划（编号：UNPYSCT-2020084）
Last Update: 2024-01-30