中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

Expression of CXCL10 and CXCL12 in gallbladder carcinoma and their mechanism of action in tumor invasion

DOI: 10.12449/JCH241120
Research funding:

Hubei Provincial Natural Science Foundation (2021CFB001)

More Information
  • Corresponding author: HU Hua, ydiyaya@163.com (ORCID: 0009-0000-0904-2694)
  • Received Date: 2024-02-28
  • Accepted Date: 2024-05-10
  • Published Date: 2024-11-25
  •   Objective  To investigate the expression levels of CXCL10 and CXCL12 in gallbladder carcinoma and their mechanism of action in tumor invasion.  Methods  Tumor tissue samples and adjacent tissue samples were collected from 56 patients with gallbladder carcinoma who underwent surgical resection in General Hospital of Central Theater Command from April 2020 to April 2023. RT-PCR was used to measure the mRNA expression levels of CXCL10 and CXCL12 in cancerous tissue and adjacent tissue, and the correlation of the mRNA expression levels of CXCL10 and CXCL12 in cancerous tissue with clinicopathological parameters was analyzed. The human gallbladder carcinoma cell line GBC-SD was used to construct gallbladder carcinoma cells with low expression of CXCL10 and CXCL12. CCK8 assay was used to observe the effect of low expression of CXCL10 and CXCL12 on the proliferation of gallbladder carcinoma cells, Transwell assay was used to observe the effect of low expression of CXCL10 and CXCL12 on the invasion ability of gallbladder carcinoma cells, and Western blot was used to measure the expression of the PI3K/Akt pathway in gallbladder carcinoma cells. The paired t-test or independent-samples t-test was used for comparison of measurement data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups.  Results  In the patients with gallbladder carcinoma, the relative mRNA expression levels of CXCL10 and CXCL12 in cancerous tissue were significantly higher than those in adjacent tissue (CXCL10: 1.857±0.315 vs 1.024±0.203, t=16.342, P<0.05; CXCL12: 2.038±0.374 vs 1.064±0.221, t=16.778, P<0.05). There were significant differences in the relative mRNA expression levels of CXCL10 and CXCL12 between the patients with different TNM stages, presence or absence of lymph node metastasis or distant metastasis, and tumor diameters (all P<0.05). Compared with the control group and the si-RNA group, the si-CXCL10 group had significantly lower relative mRNA and protein expression levels of CXCL10 and CXCL12, CCK-8 absorbance values, number of cell migration, and protein expression levels of p-PI3K and p-Akt (all P<0.05).  Conclusion  There are increases in the expression of CXCL10 and CXCL12 in gallbladder carcinoma tissue, and the proliferation and invasion of gallbladder carcinoma cells are significantly inhibited after inhibition of the expression of CXCL10 and CXCL12, which might be associated with the inhibition of the phosphorylation of the PI3K/Akt pathway.

     

  • [1]
    ROA JC, BASTURK O, ADSAY V. Dysplasia and carcinoma of the gallbladder: Pathological evaluation, sampling, differential diagnosis and clinical implications[J]. Histopathology, 2021, 79( 1): 2- 19. DOI: 10.1111/his.14360.
    [2]
    GIRALDO NA, DRILL E, SATRAVADA BA, et al. Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention[J]. Clin Cancer Res, 2022, 28( 24): 5359- 5367. DOI: 10.1158/1078-0432.CCR-22-1954.
    [3]
    LIU ZX, ZHOU SB, ZHANG ZY, et al. SDC1 knockdown promotes invasion and migration of gallbladder cancer cells via ERK signaling pathway[J]. J Mod Oncol, 2021, 29( 21): 3726- 3731. DOI: 10.3969/j.issn.1672-4992.2021.21.006.

    刘子祥, 周少波, 张子艳, 等. 沉默SDC1通过ERK信号通路促进胆囊癌细胞的侵袭和迁移[J]. 现代肿瘤医学, 2021, 29( 21): 3726- 3731. DOI: 10.3969/j.issn.1672-4992.2021.21.006.
    [4]
    KORBECKI J, KOJDER K, KAPCZUK P, et al. The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors-a review of literature[J]. Int J Mol Sci, 2021, 22( 2): 843. DOI: 10.3390/ijms22020843.
    [5]
    SUN XT, HE XK, ZHANG Y, et al. Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism[J]. Gut, 2022, 71( 1): 129- 147. DOI: 10.1136/gutjnl-2020-322744.
    [6]
    Biliary Surgery Group of Surgery Branch of Chinese Medical Association. Guideline for the diagnosis and treatment of gallbladder carcinoma(2015 edition)[J]. J Clin Hepatol, 2016, 32( 3): 411- 419. DOI: 10.3969/j.issn.1001-5256.2016.03.002.

    中华医学会外科学分会胆道外科学组. 胆囊癌诊断和治疗指南(2015版)[J]. 临床肝胆病杂志, 2016, 32( 3): 411- 419. DOI: 10.3969/j.issn.1001-5256.2016.03.002.
    [7]
    YUAN B, ZHAO XF, WANG X, et al. Patient-derived organoids for personalized gallbladder cancer modelling and drug screening[J]. Clin Transl Med, 2022, 12( 1): e678. DOI: 10.1002/ctm2.678.
    [8]
    LIU YB, CHEN W. Current situation and prospect in the clinical treatment of gallbladder cancer[J]. Chin J Dig Surg, 2023, 22( 1): 81- 88. DOI: 10.3760/cma.j.cn115610-20230109-00013.

    刘颖斌, 陈炜. 胆囊癌临床治疗的现状与展望[J]. 中华消化外科杂志, 2023, 22( 1): 81- 88. DOI: 10.3760/cma.j.cn115610-20230109-00013.
    [9]
    KAMAYA A, FUNG C, SZPAKOWSKI JL, et al. Management of incidentally detected gallbladder polyps: Society of radiologists in ultrasound consensus conference recommendations[J]. Radiology, 2022, 305( 2): 277- 289. DOI: 10.1148/radiol.213079.
    [10]
    WANG LM, XU MF, KAO CY, et al. Small molecule JQ1 promotes prostate cancer invasion via BET-independent inactivation of FOXA1[J]. J Clin Invest, 2020, 130( 4): 1782- 1792. DOI: 10.1172/JCI126327.
    [11]
    WAN GQ, LIU YH, ZHU J, et al. SLFN5 suppresses cancer cell migration and invasion by inhibiting MT1-MMP expression via AKT/GSK-3β/β-catenin pathway[J]. Cell Signal, 2019, 59: 1- 12. DOI: 10.1016/j.cellsig.2019.03.004.
    [12]
    LEI JJ, ZHANG J, ZHANG D, et al. Research progress of perineural invasion in gallbladder cancer[J]. Chin J Dig Surg, 2023, 22( 7): 933- 937. DOI: 10.3760/cma.j.cn115610-20230606-00266.

    雷建军, 张健, 张东, 等. 胆囊癌神经浸润研究进展[J]. 中华消化外科杂志, 2023, 22( 7): 933- 937. DOI: 10.3760/cma.j.cn115610-20230606-00266.
    [13]
    ZHANG GL, LUO X, ZHANG W, et al. CXCL-13 regulates resistance to 5-fluorouracil in colorectal cancer[J]. Cancer Res Treat, 2020, 52( 2): 622- 633. DOI: 10.4143/crt.2019.593.
    [14]
    YANG YR, LI JY, LEI WR, et al. CXCL12-CXCR4/CXCR7 axis in cancer: From mechanisms to clinical applications[J]. Int J Biol Sci, 2023, 19( 11): 3341- 3359. DOI: 10.7150/ijbs.82317.
    [15]
    HEIDEGGER I, FOTAKIS G, OFFERMANN A, et al. Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer[J]. Mol Cancer, 2022, 21( 1): 132. DOI: 10.1186/s12943-022-01597-7.
    [16]
    ZHANG YY, LI J, NIU YX, et al. Expression of CXC chemokine ligand 13 in cervical cancer and its effect on proliferation and migration of cervical cancer cells[J]. Chin J Gerontol, 2023, 43( 10): 2534- 2537. DOI: 10.3969/j.issn.1005-9202.2023.10.062.

    张燕怡, 李娟, 牛煜欣, 等. 宫颈癌中CXC趋化因子配体13表达及其对宫颈癌细胞增殖和迁移的影响[J]. 中国老年学杂志, 2023, 43( 10): 2534- 2537. DOI: 10.3969/j.issn.1005-9202.2023.10.062.
    [17]
    ZHOU Y, SHEN XN, CHEN ZH, et al. Expression and clinical significance of CC chemokine receptor 4 in colorectal cancer[J]. China Med Herald, 2023, 20( 11): 19- 22, 36. DOI: 10.20047/j.issn1673-7210.2023.11.04.

    周元, 沈徐宁, 陈治横, 等. 结直肠癌中CC趋化因子受体4的表达及临床意义[J]. 中国医药导报, 2023, 20( 11): 19- 22, 36. DOI: 10.20047/j.issn1673-7210.2023.11.04.
    [18]
    CHANG XD, LI HY, CHEN J, et al. The role and mechanism of human umbilical cord-derived mesenchymal stem cells in invasive of human pancreatic cancer cells[J]. Clin J Med Off, 2022, 50( 12): 1211- 1214. DOI: 10.16680/j.1671-3826.2022.12.01.

    常旭东, 李宏宇, 陈江, 等. 人脐带间充质干细胞对人胰腺癌细胞侵袭能力调控作用及机制研究[J]. 临床军医杂志, 2022, 50( 12): 1211- 1214. DOI: 10.16680/j.1671-3826.2022.12.01.
    [19]
    CHEN DL, SHENG H, ZHANG DS, et al. The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p[J]. Mol Cancer, 2021, 20( 1): 166. DOI: 10.1186/s12943-021-01475-8.
    [20]
    D’ALTERIO C, GIARDINO A, SCOGNAMIGLIO G, et al. CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in pancreatic cancer: CXCL12 predicts survival of radically resected patients[J]. Cells, 2022, 11( 21): 3340. DOI: 10.3390/cells11213340.
    [21]
    HIRTH M, GANDLA J, HÖPER C, et al. CXCL10 and CCL21 promote migration of pancreatic cancer cells toward sensory neurons and neural remodeling in tumors in mice, associated with pain in patients[J]. Gastroenterology, 2020, 159( 2): 665- 681. e 13. DOI: 10.1053/j.gastro.2020.04.037.
    [22]
    GLAVIANO A, FOO ASC, LAM HY, et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer[J]. Mol Cancer, 2023, 22( 1): 138. DOI: 10.1186/s12943-023-01827-6.
    [23]
    EDIRIWEERA MK, TENNEKOON KH, SAMARAKOON SR. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance[J]. Semin Cancer Biol, 2019, 59: 147- 160. DOI: 10.1016/j.semcancer.2019.05.012.
  • Relative Articles

    [1]Xueying LIU, Huihui SHI, Haowen WANG, Tao YANG. The material basis and toxic mechanism of herb-induced liver injury[J]. Journal of Clinical Hepatology, 2024, 40(8): 1512-1518. doi: 10.12449/JCH240802
    [2]Chenghai LIU. Research advances and challenges in herb-induced liver injury[J]. Journal of Clinical Hepatology, 2024, 40(8): 1505-1511. doi: 10.12449/JCH240801
    [3]Yinuo DONG, Yang ZHI, Jieting TANG, Yimin MAO. Diagnosis of herb-induced liver injury: Challenges in practice[J]. Journal of Clinical Hepatology, 2024, 40(8): 1533-1537. doi: 10.12449/JCH240805
    [4]Tingting HE, Zhaofang BAI, Jiabo WANG, Xiaohe XIAO. Phenotypic characteristics and toxicological mechanisms of herb-induced liver injury[J]. Journal of Clinical Hepatology, 2024, 40(8): 1525-1532. doi: 10.12449/JCH240804
    [5]Xin SUN, Qiong LUO, Tao YANG, Chenghai. LIU. Management and treatment of herb-induced liver injury[J]. Journal of Clinical Hepatology, 2024, 40(8): 1538-1542. doi: 10.12449/JCH240806
    [6]Hui ZHENG, Rong SUN. Influence of combined drug administration on herb-induced liver injury[J]. Journal of Clinical Hepatology, 2024, 40(8): 1519-1524. doi: 10.12449/JCH240803
    [7]Zhaofang BAI, Xiaoyan ZHAN, Guiji LYU, Yongping YANG. Blocking and reversing liver fibrosis with traditional Chinese medicine compound prescriptions: Beyond the known frontiers[J]. Journal of Clinical Hepatology, 2023, 39(2): 273-277. doi: 10.3969/j.issn.1001-5256.2023.02.004
    [8]Junhong LIU, Xinyu LI, Miaolei WANG, Boya FU, Linman LI, Hui FANG. Advantages and characteristics of traditional Chinese medicine in the treatment of liver fibrosis[J]. Journal of Clinical Hepatology, 2023, 39(2): 267-272. doi: 10.3969/j.issn.1001-5256.2023.02.003
    [9]Ying FENG, Ke SHI, Xiaohua ZHANG, Li YANG, Xianbo. WANG. Effect of anti-liver fibrosis traditional Chinese medicine therapy on the prognosis of patients with liver cirrhosis and superior mesenteric venous thrombosis[J]. Journal of Clinical Hepatology, 2022, 38(7): 1534-1539. doi: 10.3969/j.issn.1001-5256.2022.07.015
    [10]Luo Qiong, Zhu GeRui, Gu HongTu, Liu Kun, Chen GaoFeng, Xing Feng, Tao YanYan, Liu ChengHai. Liver histopathological features of patients with drug-induced liver injury due to Chinese herbal medicine or Western medicine: A comparative analysis of 50 cases[J]. Journal of Clinical Hepatology, 2020, 36(3): 596-601. doi: 10.3969/j.issn.1001-5256.2020.03.025
    [11]Liu ChengHai, Zhao ZhiMin, Lyu Jing. Advances in the understanding and treatment of liver fibrosis in traditional Chinese medicine[J]. Journal of Clinical Hepatology, 2019, 35(4): 728-733. doi: 10.3969/j.issn.1001-5256.2019.04.006
    [12]Sheng QingShou, Lai GuoQuan, Yu XueJing, Wei Cui. The role of traditional Chinese medicine in regulating cytokines associated with liver fibrosis[J]. Journal of Clinical Hepatology, 2018, 34(12): 2677-2680. doi: 10.3969/j.issn.1001-5256.2018.12.037
    [13]Chen Jun. Drug-induced liver injury caused by Chinese herbal medicine cannot be neglected[J]. Journal of Clinical Hepatology, 2018, 34(6): 1169-1171. doi: 10.3969/j.issn.1001-5256.2018.06.006
    [14]Liu ChengHai, Zhu ChunWu. Epidemic features, major causes, and diagnostic evaluation of herb-induced liver injury[J]. Journal of Clinical Hepatology, 2017, 33(5): 829-832. doi: 10.3969/j.issn.1001-5256.2017.05.007
    [15]Zhu Yun, Wang RuiLin, Sun XueYing, Yu SiMiao, Jing Jing, Wang JiaBo, He TingTing, Huang YiXue, Wang LiPing, Sun YongQiang. Guiding significance of Guideline for diagnosis and treatment of herb-induced liver injury in clinical diagnosis: a retrospective analysis[J]. Journal of Clinical Hepatology, 2016, 32(11): 2159-2162. doi: 10.3969/j.issn.1001-5256.2016.11.032
    [16]Branch of Hepatobiliary Diseases, China Association of Chinese Medicine, Branch of Chinese Patent Medicine, China Association of Chinese Medicine. Guideline for diagnosis and treatment of herb-induced liver injury[J]. Journal of Clinical Hepatology, 2016, 32(5): 835-843. doi: 10.3969/j.issn.1001-5256.2016.05.003
    [17]Li Yang, Xu JianMing. Clinical analysis of 11 cases of hepatic veno-occlusive disease caused by Chinese herbal medicine[J]. Journal of Clinical Hepatology, 2011, 27(2): 140-142.
    [19]Shen FengJun, Yin ChengHong, Ma Hong, Ma XueMei, Jia JiDong, Wang BaoEn, Zhu YueKe, Liu TianHui. Expression of angiotensin Ⅱ type 1 receptors mRNA in rat experimental biliary fibrosis[J]. Journal of Clinical Hepatology, 2002, 18(5): 279-281.
  • 加载中
    Created with Highcharts 5.0.7Chart context menuAccess Class DistributionFULLTEXT: 27.3 %FULLTEXT: 27.3 %META: 65.2 %META: 65.2 %PDF: 7.5 %PDF: 7.5 %FULLTEXTMETAPDF
    Created with Highcharts 5.0.7Chart context menuAccess Area Distribution其他: 5.0 %其他: 5.0 %其他: 0.3 %其他: 0.3 %Central District: 0.3 %Central District: 0.3 %China: 0.5 %China: 0.5 %Kao-sung: 0.3 %Kao-sung: 0.3 %Tiruchi: 0.3 %Tiruchi: 0.3 %上海: 5.8 %上海: 5.8 %佛山: 0.3 %佛山: 0.3 %兰州: 0.8 %兰州: 0.8 %北京: 2.3 %北京: 2.3 %南京: 1.5 %南京: 1.5 %南宁: 0.5 %南宁: 0.5 %卡纳塔克: 0.3 %卡纳塔克: 0.3 %合肥: 0.3 %合肥: 0.3 %呼和浩特: 0.3 %呼和浩特: 0.3 %咸阳: 0.3 %咸阳: 0.3 %哥伦布: 0.3 %哥伦布: 0.3 %圣安东尼奥: 0.3 %圣安东尼奥: 0.3 %大连: 0.3 %大连: 0.3 %天津: 0.3 %天津: 0.3 %安阳: 0.3 %安阳: 0.3 %宣城: 0.8 %宣城: 0.8 %山景城: 0.3 %山景城: 0.3 %常州: 0.3 %常州: 0.3 %常德: 0.8 %常德: 0.8 %广州: 0.5 %广州: 0.5 %张家口: 4.8 %张家口: 4.8 %得梅因: 0.3 %得梅因: 0.3 %德阳: 0.3 %德阳: 0.3 %成都: 0.3 %成都: 0.3 %日照: 0.5 %日照: 0.5 %杭州: 0.5 %杭州: 0.5 %武汉: 0.5 %武汉: 0.5 %沈阳: 0.3 %沈阳: 0.3 %泰州: 0.3 %泰州: 0.3 %洛阳: 0.3 %洛阳: 0.3 %海得拉巴: 0.8 %海得拉巴: 0.8 %深圳: 0.5 %深圳: 0.5 %温州: 0.3 %温州: 0.3 %焦作: 0.3 %焦作: 0.3 %眉山: 0.3 %眉山: 0.3 %石家庄: 0.3 %石家庄: 0.3 %科泽科德: 0.3 %科泽科德: 0.3 %红河: 0.5 %红河: 0.5 %芒廷维尤: 29.3 %芒廷维尤: 29.3 %芝加哥: 3.8 %芝加哥: 3.8 %苏州: 0.3 %苏州: 0.3 %莫斯科: 0.5 %莫斯科: 0.5 %衡水: 0.3 %衡水: 0.3 %西宁: 11.0 %西宁: 11.0 %西安: 0.5 %西安: 0.5 %诺沃克: 0.3 %诺沃克: 0.3 %贵阳: 0.5 %贵阳: 0.5 %赣州: 0.3 %赣州: 0.3 %运城: 0.8 %运城: 0.8 %遂宁: 0.5 %遂宁: 0.5 %郑州: 4.5 %郑州: 4.5 %重庆: 1.3 %重庆: 1.3 %金华: 0.3 %金华: 0.3 %长春: 12.8 %长春: 12.8 %长沙: 0.3 %长沙: 0.3 %其他其他Central DistrictChinaKao-sungTiruchi上海佛山兰州北京南京南宁卡纳塔克合肥呼和浩特咸阳哥伦布圣安东尼奥大连天津安阳宣城山景城常州常德广州张家口得梅因德阳成都日照杭州武汉沈阳泰州洛阳海得拉巴深圳温州焦作眉山石家庄科泽科德红河芒廷维尤芝加哥苏州莫斯科衡水西宁西安诺沃克贵阳赣州运城遂宁郑州重庆金华长春长沙

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(5)

    Article Metrics

    Article views (214) PDF downloads(20) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return