切换至 "中华医学电子期刊资源库"

中华肝脏外科手术学电子杂志 ›› 2018, Vol. 07 ›› Issue (02) : 147 -151. doi: 10.3877/cma.j.issn.2095-3232.2018.02.015

所属专题: 文献

基础研究

端粒酶调控因子PinX1抑制肝癌细胞增殖与侵袭
李瑞曦1, 姚志成2, 熊志勇2, 周伯宣1, 徐见亮1, 胡昆鹏2, 范伟明1, 梁豪1, 邓美海1,()   
  1. 1. 510630 广州,中山大学附属第三医院肝胆外科
    2. 510530 广州,中山大学附属第三医院岭南医院普通外科
  • 收稿日期:2018-01-15 出版日期:2018-04-10
  • 通信作者: 邓美海
  • 基金资助:
    广东省自然科学基金(2016A030313848,S2013010016015); 广州市科技计划项目(2013J4100061)

Telomerase regulation factor PinX1 inhibits proliferation and invasion of hepatoma cells

Ruixi Li1, Zhicheng Yao2, Zhiyong Xiong2, Boxuan Zhou1, Jianliang Xu1, Kunpeng Hu2, Weiming Fan1, Hao Liang1, Meihai Deng1,()   

  1. 1. Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    2. Department of General Surgery, Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510530, China
  • Received:2018-01-15 Published:2018-04-10
  • Corresponding author: Meihai Deng
  • About author:
    Corresponding author: Deng Meihai, Email:
引用本文:

李瑞曦, 姚志成, 熊志勇, 周伯宣, 徐见亮, 胡昆鹏, 范伟明, 梁豪, 邓美海. 端粒酶调控因子PinX1抑制肝癌细胞增殖与侵袭[J]. 中华肝脏外科手术学电子杂志, 2018, 07(02): 147-151.

Ruixi Li, Zhicheng Yao, Zhiyong Xiong, Boxuan Zhou, Jianliang Xu, Kunpeng Hu, Weiming Fan, Hao Liang, Meihai Deng. Telomerase regulation factor PinX1 inhibits proliferation and invasion of hepatoma cells[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(02): 147-151.

目的

探讨端粒酶调控因子PinX1对肝癌细胞增殖和侵袭能力的影响。

方法

构建稳定表达PinX1的肝癌细胞PinX1-7721(实验组)及其对照细胞VECTOR-7721(对照组)。RT-PCR法检测PinX1 mRNA的表达,CCK-8法和平板克隆形成实验检测肝癌细胞的增殖能力和克隆形成能力,Transwell实验检测肝癌细胞的侵袭能力。实验数据比较采用t检验。

结果

实验组细胞PinX1 mRNA表达量为(13.9±2.0)×10-3,明显高于对照组的(1.1±0.2)×10-3t=10.98,P<0.05)。实验组细胞1~7 d的A450值分别为0.260±0.004、0.340±0.008、0.450±0.040、0.500±0.020、0.730±0.030、1.350±0.040、1.640±0.050,明显低于对照组的0.280±0.009、0.410±0.007、0.680±0.044、0.730±0.029、0.850±0.070、1.700±0.020、2.080±0.280(t=-5.82,-12.99,-6.36,-5.96,-28.42,-18.98,-5.08;P<0.05)。平板克隆实验结果显示实验组细胞克隆形成数目为(143±32)个,明显低于对照组的(305±25)个(t=-6.91,P<0.05)。Transwell实验结果显示实验组细胞穿膜数目为(230±16)个,明显低于对照组的(650±30)个(t=-21.40,P<0.05)。

结论

PinX1可抑制肝癌细胞的增殖和侵袭能力。

Objective

To explore the impact of telomerase regulation factor PinX1 to the proliferation and invasion ability of hepatoma cells.

Methods

Hepatoma cells PinX1-7721 (experimental group) with stable expression of PinX1 as well as control cell VECTOR-7721 (control group) were constructed. The expression of PinX1 mRNA was detected by RT-PCR. The proliferation ability and clonality of hepatoma cells were detected by CCK-8 method and plate clonality assay, and the invasion ability of hepatoma cells by Transwell assay. Comparison of the experiment data was conducted by t test.

Results

Expression level of PinX1 mRNA in experiment group was (13.9±2.0)×10-3, which was significantly higher than (1.1±0.2)×10-3 in control group (t=10.98, P<0.05). A450 of the cells on 1-7 d in experiment group was respectively 0.260±0.004, 0.340±0.008, 0.450±0.040, 0.500±0.020, 0.730±0.030, 1.350±0.040 and 1.640±0.050, which were significantly lower than 0.280±0.009, 0.410±0.007, 0.680±0.044, 0.730±0.029, 0.850±0.070, 1.700±0.020 and 2.080±0.280 in control group (t=-5.82, -12.99, -6.36, -5.96, -28.42, -18.98, -5.08; P<0.05). The plate clonality assay results showed that the clone formation quantity of cells in experiment group was 143±32, which was significantly lower than 305±25 in control group (t=-6.91, P<0.05). Transwell assay results showed that the quantity of trans-membrane cell in experiment group was 230±16, which was significantly lower than 650±30 in control group (t=-21.40, P<0.05).

Conclusion

PinX1 could inhibit the proliferation and invasion ability of hepatoma cells.

图1 实验组与对照组肝癌细胞生长曲线
图2 实验组与对照组肝癌细胞平板克隆形成实验
图3 实验组与对照组肝癌细胞Transwell实验结果(×100)
[1]
Herz C, Hertrampf A, Zimmermann S, et al. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC[J]. J Cell Mol Med, 2014, 18(12):2393-2403.
[2]
Venook AP, Papandreou C, Furuse J, et al. The incidence and epidemiology of hepatocellular carcinoma:a global and regional perspective[J]. Oncologist, 2010, 15 Suppl 4:5-13.
[3]
吴小溪,米志宽.肝癌组织端粒酶活性与肝癌病理类型关系的研究[J].延安大学学报(医学科学版),2014,12(1):4-5.
[4]
刘霖,胡大春.端粒、端粒酶基因及其突变在肝癌发生发展中的研究进展[J].国际检验医学杂志,2015(12):1762-1765.
[5]
Kara M, Ozcagli E, Fragkiadaki P, et al. Determination of DNA damage and telomerase activity in stanozolol-treated rats[J]. Exp Ther Med, 2017, 13(2):614-618.
[6]
Arsenis NC, You T, Ogawa EF, et al. Physical activity and telomere length:impact of aging and potential mechanisms of action[J]. Oncotarget, 2017, 8(27):45008-45019.
[7]
Zhang J, Ju H, Gao JR, et al. Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene-gene and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han population[J]. Oncotarget, 2017, 8(12):20235-20243.
[8]
Armstrong CA, Tomita K. Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells[J]. Open Biol, 2017, 7(3):160338.
[9]
Cheung DH, Ho ST, Lau KF, et al. Nucleophosmin interacts with PIN2/TERF1-interacting telomerase inhibitor 1 (PinX1) and attenuates the PinX1 inhibition on telomerase activity[J]. Sci Rep, 2017(7):43650.
[10]
王荣福,康磊,徐小洁,等.端粒酶靶向的RNA标记探针在肿瘤活体显像的研究[J].北京大学学报(医学版),2013,45(2):250-254.
[11]
Park YJ, Kim EK, Bae JY, et al. Human telomerase reverse transcriptase (hTERT) promotes cancer invasion by modulating cathepsin D via early growth response (EGR)-1[J]. Cancer Lett, 2016, 370(2):222-231.
[12]
Nault JC, Mallet M, Pilati C, et al. High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions[J]. Nat Commun, 2013(4):2218.
[13]
Tahtouh R, Azzi AS, Alaaeddine N, et al. Telomerase inhibition decreases alpha-fetoprotein expression and secretion by hepatocellular carcinoma cell lines: in vitro and in vivo study[J]. PLoS One, 2015, 10(3):e0119512.
[14]
Fan XK, Yan RH, Geng XQ, et al. Biological significance of PinX1 telomerase inhibitor in esophageal carcinoma treatment[J]. Exp Ther Med, 2016, 12(4):2196-2200.
[15]
Li HL, Song J, Yong HM, et al. PinX1: structure,regulation and its functions in cancer[J]. Oncotarget, 2016, 7(40):66267-66275.
[16]
Qian D, Cheng J, Ding X, et al. PinX1 suppresses tumorigenesis by negatively regulating telomerase/telomeres in colorectal carcinoma cells and is a promising molecular marker for patient prognosis[J]. Onco Targets Ther, 2016(9):4821-4831.
[17]
Bai J, Chen YS, Mei PJ, et al. PinX1 is up-regulated and associated with poor patients' survival in gliomas[J]. Int J Clin Exp Pathol, 2015, 8(6):6952-6959.
[18]
Heng J, Zhang F, Guo X, et al. Integrated analysis of promoter methylation and expression of telomere related genes in breast cancer[J]. Oncotarget, 2017, 8(15):25442-25454.
[19]
Absalan A, Mesbah-Namin SA, Tiraihi T, et al. Cinnamaldehyde and eugenol change the expression folds of AKT1 and DKC1 genes and decrease the telomere length of human adipose-derived stem cells (hASCs):an experimental and in silico study[J]. Iran J Basic Med Sci, 2017, 20(3):316-326.
[1] 王兴, 张峰伟. 腹腔镜肝切除联合断面射频消融治疗伴微血管侵犯肝细胞癌的临床研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(05): 580-583.
[2] 魏小勇. 原发性肝癌转化治疗焦点问题探讨[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 602-607.
[3] 张其坤, 商福超, 李琪, 栗光明, 王孟龙. 联合脾切除对肝癌合并门静脉高压症患者根治性切除术后的生存获益分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 613-618.
[4] 严庆, 刘颖, 邓斐文, 陈焕伟. 微血管侵犯对肝癌肝移植患者生存预后的影响[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 624-629.
[5] 张文华, 陶焠, 胡添松. 不同部位外生型肝癌临床病理特点及其对术后肝内复发和预后影响[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 651-655.
[6] 韩宇, 张武, 李安琪, 陈文颖, 谢斯栋. MRI肝脏影像报告和数据系统对非肝硬化乙肝患者肝细胞癌的诊断价值[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 669-673.
[7] 张维志, 刘连新. 基于生物信息学分析IPO7在肝癌中的表达及意义[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 694-701.
[8] 陈安, 冯娟, 杨振宇, 杜锡林, 柏强善, 阴继凯, 臧莉, 鲁建国. 基于生物信息学分析CCN4在肝细胞癌中表达及其临床意义[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 702-707.
[9] 叶文涛, 吴忠均, 廖锐. 癌旁组织ALOX15表达与肝癌根治性切除术后预后的关系[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 708-712.
[10] 吴晨瑞, 廖锐, 贺强, 潘龙, 黄平, 曹洪祥, 赵益, 王永琛, 黄俊杰, 孙睿锐. MDT模式下肝动脉灌注化疗联合免疫靶向治疗肝细胞癌多处转移一例[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 713-716.
[11] 杜锡林, 谭凯, 贺小军, 白亮亮, 赵瑶瑶. 肝细胞癌转化治疗方式[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 597-601.
[12] 王峰杰, 王礼光, 廖珊, 刘颖, 符荣党, 陈焕伟. 腹腔镜右半肝切除术治疗肝癌的安全性与疗效[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 517-522.
[13] 张海涛, 贾哲, 马超, 张其坤, 武聚山, 郭庆良, 曾道炳, 栗光明, 王孟龙. 手术切除与射频消融治疗血管周围型单发小肝癌临床疗效分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 523-527.
[14] 吕瑶, 张婵, 陈建华, 张鸣青. 压力控制容量保证通气模式在腹腔镜肝细胞癌切除术中的应用[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 528-533.
[15] 杨秀君, 崔梦莹, 张丹, 曲仙智, 苗云皓, 盛基尧, 郑戈, 刘水, 张学文. 信迪利单抗联合仑伐替尼成功转化治疗不可切除肝癌一例[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 581-584.
阅读次数
全文


摘要