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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2014, Vol. 03 ›› Issue (04) : 247 -251. doi: 10.3877/cma.j.issn.2095-3232.2014.04.013

所属专题： 文献；

基础研究

细胞周期检测点激酶1在肝细胞癌中的表达及意义
唐云强1, 何璐1, 唐辉1, 张琼2, 洪健1,†()   
  1. 1. 510095，广州医科大学附属肿瘤医院肝胆外科
    2. 510095，广州医科大学附属肿瘤医院病理科
  • 收稿日期:2014-04-02 出版日期:2014-08-10
  • 通信作者: 洪健
  • 基金资助:
    国家自然科学基金(81201634); 广州医科大学附属肿瘤医院重大专项(2001-yz-03)

Expression and significance of cell cycle checkpoint kinase 1 in hepatocelluar carcinoma

Yunqiang Tang1, Lu He1, Hui Tang1, Qiong Zhang2, Jian Hong1,†()   

  1. 1. Department of Hepatobiliary Surgery, Cancer Center of Guangzhou Medical University, Guangzhou 510095, China
  • Received:2014-04-02 Published:2014-08-10
  • Corresponding author: Jian Hong
  • About author:
    Corresponding author: Hong Jian, Email:
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引用本文：

唐云强, 何璐, 唐辉, 张琼, 洪健. 细胞周期检测点激酶1在肝细胞癌中的表达及意义[J]. 中华肝脏外科手术学电子杂志, 2014, 03(04): 247-251.

Yunqiang Tang, Lu He, Hui Tang, Qiong Zhang, Jian Hong. Expression and significance of cell cycle checkpoint kinase 1 in hepatocelluar carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2014, 03(04): 247-251.

目的

探讨细胞周期检测点激酶1（Chk1）在肝细胞癌（肝癌）中的表达及其对肝癌侵袭能力的影响。

方法

标本来源于2005年6月至2010年6月在广州医科大学附属肿瘤医院行根治性肝切除术的127例患者的肝癌及癌旁组织。所有患者均签署知情同意书，符合医学伦理学规定。其中男116例，女11例；年龄23～77岁，中位年龄50岁。采用免疫组织化学方法检测肝癌和癌旁组织中Chk1表达，并分别采用Huh7和MHCC-97H肝癌细胞进行Transwell细胞侵袭实验。实验分为两组，Chk1抑制剂组（抑制组）加入Chk1小分子抑制剂G?6976，对照组加入0.1%二甲基亚砜（DMSO）。观察肝癌和癌旁组织中Chk1的表达情况，以及Chk1表达与临床病理学参数的关系。两组穿膜细胞数比较采用t检验，率的比较采用χ2检验。

结果

肝癌组织Chk1阳性率为80.3% （102/127），明显高于癌旁肝组织的15.0%（19/127） （χ2=108.700，P<0.05）。肿瘤数目多发、无肿瘤包膜、术后早期复发的患者肝癌组织中Chk1高表达（χ2= 6.289，4.713，5.039；P<0.05）。抑制剂组Huh7和MHCC-97H肝癌细胞的穿膜细胞数分别为（127±8）、（136±10）个，对照组相应为（174±11）、（188±13）个，抑制组明显低于对照组（t =-3.402，-3.136；P<0.05）。

结论

肝癌组织中存在Chk1高表达，Chk1高表达与肝癌的侵袭和转移有关，Chk1抑制剂可有效抑制肝癌细胞的侵袭能力。

关键词: 癌，肝细胞, 细胞周期检测点激酶, 肿瘤转移
Objective

To investigate the expression of cell cycle checkpoint kinase 1 (Chk1) and its impact on the invasion capacity of hepatocellular carcinoma (HCC).

Methods

Samples of HCC tissues and adjacent non-tumor tissues from 127 patients undergoing radical hepatectomy in Cancer Center of Guangzhou Medical University from June 2005 to June 2010 were collected. The informed consents of all patients were obtained and the ethical committee approval was received. The patients included 116 males and 11 females with age ranging from 23 to 77 years old and a median age of 50 years old. The expression of Chk1 was detected by immunohistochemistry, and Transwell cell invasion assay was performed using HCC cells Huh7 and MHCC-97H. The experiment was divided into two groups. Chk1 small-molecule inhibitor G?6976 was added in Chk1 inhibitor group (inhibitor group). Dimethyl sulfoxide (DMSO, 0.1%) was added in control group. The expression of Chk1 in HCC tissues and adjacent non-tumor tissues, the relation between Chk1 expression and clinicopathological indicators were observed. The difference of cell-membrane penetrating count in two groups was compared using t test. The comparison of rates was conducted using Chi-square test.

Results

The positive rate of Chk1 in HCC tissues [80.3% (102/127)] was significantly higher than that in adjacent non-tumor tissues [15.0% (19/127)] (χ2=108.700, P<0.05). High expression of Chk1 was observed in HCC tissues of patients with multiple tumors, non-coating tumors or early tumor recurrence after operation (χ2= 6.289, 4.713, 5.039; P<0.05). The cell-membrane penetrating counts of HCC cells Huh7 and MHCC-97H in inhibitor group (127±8, 136±10) were significantly lower than those in control group (174±11, 188±13) ( t =-3.402, -3.136; P<0.05).

Conclusions

High expression of Chk1 can be observed in HCC tissues. It’s associated with the invasion and metastasis of HCC. The Chk1 inhibitor can effectively suppress the invasion capacity of HCC cells.

Key words: Carcinoma, hepatocellular, Cell cycle checkpoint kinase, Neoplasm metastasis
图1 肝癌及癌旁组织切片
表1 肝癌组织Chk1表达与临床病理学参数的关系
参数 例数 Chk1表达 χ 2值 P值
阳性 百分率（%）
HBsAg ? ? ? 1.561 >0.05
? 阴性 12 8 67 ? ?
? 阳性 115 94 82 ? ?
AFP (μg/L) ? ? ? 0.218 >0.05
? ≤20 31 24 77 ? ?
? > 20 96 78 81 ? ?
肿瘤直径(cm) ? ? ? 1.263 >0.05
? ≤5 39 29 74 ? ?
? > 5 88 73 83 ? ?
肿瘤数目 ? ? ? 6.289 <0.05
? 单个 79 58 73 ? ?
? 多个 48 44 92 ? ?
肿瘤包膜 ? ? ? 4.713 <0.05
? 无 93 79 85 ? ?
? 有 34 23 68 ? ?
血管侵犯 ? ? ? 4.211 >0.05
? 无 97 74 76 ? ?
? 有 30 28 93 ? ?
组织学分化程度 ? ? ? 1.409 >0.05
? Ⅰ～Ⅱ级 73 56 77 ? ?
? Ⅲ～Ⅳ级 54 46 85 ? ?
BCLC分期 ? ? ? 3.473 >0.05
? 0～A期 70 56 80 ? ?
? B期 27 19 70 ? ?
? C期 30 27 90 ? ?
术后早期复发 ? ? ? 5.039 <0.05
? 无 42 29 69 ? ?
? 有 85 73 86 ? ?
[1]
吴孟超．肝癌在中国[J/CD]．中华肝脏外科手术学电子杂志，2012, 1(1):3-4.
[2]
Ma CX, Janetka JW, Piwnica-Worms H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics[J]. Trends Mol Med, 2011, 17(2):88-96.
[3]
Russell MR, Levin K, Rader J, et al. Combination therapy targeting the Chk1 and Wee1 kinases shows therapeutic efficacy in neuroblastoma[J]. Cancer Res, 2013, 73(2):776-784.
[4]
Hong J, Hu K, Yuan Y, et al. CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma[J]. J Clin Invest, 2012, 122(6):2165-2175.
[5]
He L, Zhou X, Qu C, et al. Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients[J]. Med Oncol, 2013, 30(4):707-713.
[6]
Hoshida Y, Toffanin S, Lachenmayer A, et al. Molecular classification and novel targets in hepatocellular carcinoma: recent advancements[J]. Semin Liver Dis, 2010, 30(1):35-51.
[7]
Yin J, Li N, Han Y, et al. Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study[J]. J Clin oncol, 2013, 31(29):3647-3655.
[8]
Xie B, Wang DH, Spechler SJ. Sorafenib for treatment of hepatocellular carcinoma: a systematic review[J]. Dig Dis Sci, 2012, 57(5):1122-1129.
[9]
Xiao Y, Ramiscal J, Kowanetz K, et al. Identification of preferred chemotherapeutics for combining with a CHK1 inhibitor[J]. Mol Cancer Ther, 2013, 12(11):2285-2295.
[10]
Engelke CG, Parsels LA, Qian Y, et al. Sensitization of pancreatic cancer to chemoradiation by the Chk1 inhibitor MK8776[J]. Clin Cancer Res, 2013, 19(16):4412-4421.
[11]
Dent P, Tang Y, Yacoub A, et al. CHK1 inhibitors in combination chemotherapy: thinking beyond the cell cycle[J]. Mol Interv, 2011, 11(2):133-140.
[12]
Verlinden L, Vanden Bempt I, Eelen G, et al. The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor /progesterone receptor /HER-2 breast carcinomas[J]. Cancer Res, 2007, 67(14):6574-6581.
[13]
丛文铭，吴孟超．肝癌术后复发发生机制及临床病理学意义[J]．中国实用外科杂志，2012,32(10):809-811.
[14]
Xu J, Li Y, Wang F, et al. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer[J]. Oncogene, 2013, 32(8):976-987.
[15]
Wang Y, Shenouda S, Baranwal S, et al. Integrin subunits alpha5 and alpha6 regulate cell cycle by modulating the chk1 and Rb/E2F pathways to affect breast cancer metastasis[J]. Mol Cancer, 2011(10):84.
[16]
Krishnamachary B, Glunde K, Wildes F, et al. Noninvasive detection of lentiviral-mediated choline kinase targeting in a human breast cancer xenograft[J]. Cancer Res, 2009, 69(8):3464-3471.
[17]
Sun X, Liu B, Wang J, et al. Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway[J]. Int J Oncol, 2013, 42(2):683-689.
[18]
Booth L, Cruickshanks N, Ridder T, et al. PARP and CHK inhibitors interact to cause DNA damage and cell death in mammary carcinoma cells[J]. Cancer Biol Ther, 2013, 14(5):458-465.
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