|Table of Contents|

Influences of recombinant human endostatin combined with TACE on microvessel density and Notch pathway of rabbit model of VX-2 liver cancer

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

Issue:
2023 08
Page:
1428-1434
Research Field:
Publishing date:

Info

Title:
Influences of recombinant human endostatin combined with TACE on microvessel density and Notch pathway of rabbit model of VX-2 liver cancer
Author(s):
YANG BoLI YuweiPAN FengLIU Yuyu
Department of Interventional Medicine,Affiliated Hospital of Southwest Medical University,Sichuan Luzhou 646000,China.
Keywords:
recombinant human endostatintranscatheter arterial chemoembolizationliver cancerdrosophila double wing margin nicked homologous gene (Notch) pathwaymicrovessel density
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2023.08.008
Abstract:
Objective:To investigate the regulatory effect of recombinant human endostatin (rhES) combined with transcatheter arterial chemoembolization (TACE) on drosophila double wing margin nicked homologous gene (Notch) pathway and its influence on microvessel density (MVD) of the rabbit model of VX-2 liver cancer.Methods:Fifty of sixty New Zealand white rabbits were randomly selected to establish the VX-2 liver cancer model by tumor implantation,and they were grouped into model group,TACE group,TACE+rhES group (TACE+rhES solution in 0.75 mg/kg),Notch activator jagged1 group (TACE+jagged1 solution in 13 ng/kg),TACE+rhES+jagged1 group (TACE+rhES solution in 0.75 mg/kg+jagged1 solution in 13 ng/kg),with 10 rabbits in each group,and the 10 rabbits without model were served as normal control group.After 2 weeks of treatment,CT imaging was performed to obtain the blood flow (BF),blood volume (BV) and capillary surface permeability area (PS) around the tumor of rabbits.The weight of rabbits was weighed,the rabbits were sacrificed and their livers were taken to calculate the liver index and tumor volume.Immunohistochemistry was used to detect the MVD of liver.Western blot was used to detect the relative protein expression levels of Notch,Notch ligand (jagged1),vascular endothelial growth factor (VEGF),and activated protein 1 (AP-1) in non-necrotic liver tissue around the tumor.Results:Compared with the normal control group,the rabbits in the model group had decreased diet,decreased activity and apathy,and the tumor nodules were dark red with pathological damages such as necrosis,liquefaction and cystic changes.The liver index,tumor volume,MVD,protein expressions of Notch,jagged1,VEGF and AP-1 were higher (P<0.05),and the body weight and levels of BF,BV and PS were lower (P<0.05).Compared with the model group,the tumor nodule in TACE group was milky white,and the tumor volume was obviously lower (P<0.05),and there was no obvious difference in other indicators (P>0.05).The degrees of mental depression and tumor necrosis in jagged1 group increased,and the liver index,tumor volume,MVD,protein expressions of Notch,jagged1,VEGF and AP-1 were higher (P<0.05),and the body weight and levels of BF,BV and PS were lower (P<0.05).The diet and spirit of rabbits in TACE+rhES group were improved,and the degree of tumor necrosis was reduced,the liver index,tumor volume,protein expressions of Notch,jagged1,VEGF and AP-1 were lower (P<0.05),and the body weight and the levels of BF,BV and PS were higher (P<0.05).Compared with those in TACE+rhES group,the above indexes in TACE+rhES+jagged1 group showed opposite trends,and the difference was statistically obvious (P<0.05).Conclusion:The combined therapy of TACE+rhES can inhibit tumor angiogenesis in rabbit model of liver cancer by inhibiting the activation of Notch/jagged1 signaling pathway.

References:

[1]ZHANG W,WANG J,GAO J,et al.Prediagnostic level of dietary and urinary isoflavonoids in relation to risk of liver cancer in Shanghai,China[J].Cancer Epidemiol Biomarkers Prev,2019,28(10):1712-1719.
[2]马婧嶔,颜志平.肝癌介入治疗进一步思考[J].介入放射学杂志,2019,28(6):507-510. MA JQ,YAN ZP.Further consideration on interventional therapy of liver cancer[J].Journal of Interventional Radiology,2019,28(6):507-510.
[3]尹丹萍,董俊峰.肝动脉化疗栓塞术治疗肝癌的疗效分析[J].中西医结合心血管病电子杂志,2018,6(8):3-4. YIN DP,DONG JF.Therapeutic effect of transeatheter arterial chemoembolization in the treatment of primary hepatocellular carcinoma[J].Cardiovascular Disease Electronic Journal of Integrated Traditional Chinese and Western Medicine,2018,6(8):3-4.
[4]张庆,于德升,马克波,等.原发性肝癌术后TACE治疗次数对患者生存及肿瘤复发的影响[J].中国现代普通外科进展,2018,21(9):741-743. ZHANG Q,YU DS,MA KB,et al.Effect of TACE treatment times on patients' survival and tumor recurrence after primary liver cancer surgery[J].Chinese Journal of Current Advances in General,2018,21(9):741-743.
[5]韩楠楠,姜秋颖,李里,等.重组人血管内皮抑制素(恩度)临床机制的研究进展[J].现代生物医学进展,2019,19(15):2993-2995. HAN NN,JIANG QY,LI L,et al.Advance in the clinical mechanism of recombinant human endostatin[J].Progress in Modern Biomedicine,2019,19(15):2993-2995.
[6]杨柳青,吴东,张鸣,等.重组人血管内皮抑制素联合经导管动脉栓塞化疗治疗中期肝癌患者的临床效果和安全性分析[J].山西医药杂志,2018,47(18):2178-2180. YANG LQ,WU D,ZHANG M,et al.Clinical efficacy and safety of recombinant human endostatin combined with transcatheter arterial chemoembolization in the treatment of patients with middle-term liver cancer[J].Shanxi Medical Journal,2018,47(18):2178-2180.
[7]CAI L,LUO L,TANG Z,et al.Combined antitumor effects of 1,25-dihydroxy vitamin D3 and notch inhibitor in liver cancer[J].Oncol Rep,2018,40(3):1515-1524.
[8]QI C,LIN Y,LIN D.The effect of Shu Xue Tong treatment on random skin flap survival via the VEGF-notch/Dll4 signaling pathway[J].J Invest Surg,2020,33(7):615-620.
[9]吴海东,张春堂,王建华,等.两种不同方式建立兔小肝癌模型的比较研究[J].医学影像学杂志,2019,29(7):1227-1220. WU HD,ZHANG CT,WANG JH,et al.Comparison of two different ways in establishing the rabbit small liver cancer[J].Journal of Medical Imaging,2019,29(7):1227-1220.
[10]卞超凡,吕维富,俞傲,等.兔VX2肝癌经导管肝动脉栓塞化疗术后肠道通透性、脂多糖和Toll样受体4改变的实验研究[J].中华放射学杂志,2020,54(5):491-494. BIAN CF,LYU WF,YU A,et al.An experimental study on the alteration of intestinalpermeability,lipopolysaccharide and Toll-like receptor 4 in rabbit VX2 liver cancer after transarterial chemoembolization[J].Chinese Journal of Radiology,2020,54(5):491-494.
[11]赵登玲,邓钢,李光超,等.经肝动脉灌注重组人血管内皮抑制素联合TACE治疗兔VX 2肝癌及肿瘤血管生成的评估[J].肿瘤,2008,28(3):211-215. ZHAO DL,DENG G,LI GC,et al.Transcatheter hepatic artery infusion with recombinant human endostatin combined with TACE for rabbit VX2 hepatoma and evaluation on angiogenesis by CT perfusion[J].Tumor,2008,28(3):211-215.
[12]吴绍军,刘俊才,左银龙,等.Notch信号通路在膝骨关节炎软骨细胞凋亡中的作用研究[J].华西医学,2018,33(9):115-120. WU SJ,LIU JC,ZUO YL,et al.The effect of Notch signaling pathway on apoptosis of articular chondrocytes in knee osteoarthritis[J].West China Medical Journal,2018,33(9):115-120.
[13]刘洪敬,冯将,杨建军,等.以TACE为主综合治疗原发性肝癌的研究进展[J].延安大学学报(医学科学版),2019,17(3):82-86. LIU HJ,FENG J,YANG JJ,et al.Research progress in comprehensive treatment of primary liver cancer based on TACE[J].Journal of Yan'an University(Medical Science Edition),2019,17(3):82-86.
[14]李海涛,解皓,吴文娟,等.经肝动脉化疗栓塞术联合重组人血管内皮抑制素对兔VX_2肝移植瘤生长及转移的影响[J].实用放射学杂志,2010,26(1):110-114. LI HT,JIE H,WU WJ,et al.The effect of recombinant human endostatin combined with TACE on the growth and metastases of the implanted hepatic tumors in rabbits[J].Journal of Practical Radiology,2010,26(1):110-114.
[15]JESINA D.Alagille syndrome:an overview[J].Neonatal Netw,2017,36(6):343-347.
[16]OON CE,BRIDGES E,SHELDON H,et al.Role of Delta-like 4 in jagged1-induced tumour angiogenesis and tumour growth[J].Oncotarget,2017,8(25):40115-40131.
[17]SUBRAMANIAM N,PETRIK JJ,VICKARYOUS MK,et al.VEGF,FGF-2 and TGFβ expression in the normal and regenerating epidermis of geckos:implications for epidermal homeostasis and wound healing in reptiles[J].J Anat,2018,232(5):768-782.
[18]XIU MX,LIU YM,KUANG BH,et al.The oncogenic role of jagged1/notch signaling in cancer[J].Biomed Pharmacother,2020,129(1):1104-1116.
[19]李萍,辛彦.Jagged1/Notch通路与肿瘤血管生成的研究进展[J].现代肿瘤医学,2013,21(7):1645-1648. LI P,XIN Y.Research progress of Jagged1/Notch pathway and tumor angiogenesis[J].Modern Oncology,2013,21(7):1645-1648.

Memo

Memo:
西南医科大学校级基金资助计划项目(编号:2017-ZRQN-141)
Last Update: 1900-01-01