抑制SNAI2分子表达增强肝癌细胞的肿瘤干细胞特性和多药耐药性

肝脏 ›› 2018, Vol. 23 ›› Issue (11): 981-984.

抑制SNAI2分子表达增强肝癌细胞的肿瘤干细胞特性和多药耐药性

奚卫, 张颐豪, 魏清

201112 上海交通大学医学院附属仁济医院南院检验科

收稿日期:2018-08-27 出版日期:2018-11-30 发布日期:2020-04-28
通讯作者: 魏清,Email:weiqingjn@126.com
基金资助:
国家自然科学基金青年项目(81501813)

Inhibition of SNAI2 expression enhances tumor stem cell-like characteristics and multi-drug resistance of hepatoma cells

XI Wei, ZHANG Yi-hao, WEI Qing

Department of Clinical Laboratory, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University

Received:2018-08-27 Online:2018-11-30 Published:2020-04-28
Contact: WEI Qing, Email: weiqingjn@126.com

摘要/Abstract

摘要： 目的探究Snail家族转录抑制因子2(SNAI2)在肝细胞肝癌中的作用。方法利用shRNA慢病毒转染肝癌细胞以及细胞成球实验分析了SNAI2缺失对肝癌细胞锚定非依赖生长的影响,随后又利用CCK-8 实验检测肝癌细胞SNAI2分子缺失对多种化疗药物敏感性的影响。结果当shRNA抑制SNAI2表达时,肝癌细胞锚定非依赖性生长能力以及集落形成力均显着增加。抑制SNAI2分子表达增强了肝癌细胞对多种化疗药物的耐药性。结论 SNAI2分子通过抑制肝细胞肝癌的EMT发生和抑制多药耐药性,从而起到肿瘤抑制作用。

关键词: SNAI2, 上皮间质转换, 多药耐药, 肝细胞肝癌

Abstract: Objective The role of Snail family transcriptional repressor 2 (SNAI2) in different types of malignant tumors remains controversial. The study aimed to investigate the role of SNAI2 in hepatocellular carcinoma (HCC). Methods The shRNA lentivirus was used to transfect HCC cells and analyzed the effect of SNAI2 deletion on anchorage-independent growth of HCC cells by cell pelleting assay, and cholecystokinin-8 assay was used to detect the sensitivity of HCC cells with SNAI2 deletion to various chemotherapeutic drugs. Results When the expression of SNAI2 was inhibited by shRNA, the anchorage-independent growth ability and colony formation ability of HCC cells were significantly increased. Inhibition of SNAI2 molecule expression enhanced the resistance of HCC cells to various chemotherapeutic drugs. Conclusion The study indicated that SNAI2 plays a significant tumor suppressive role in HCC by inhibiting epithelial-mesenchymal transition and multidrug resistance.

Key words: Snail family transcriptional repressor 2, Epithelial-mesenchymal transition, Multidrug resistance, Hepatocellular carcinoma

奚卫, 张颐豪, 魏清. 抑制SNAI2分子表达增强肝癌细胞的肿瘤干细胞特性和多药耐药性[J]. 肝脏, 2018, 23(11): 981-984.

XI Wei, ZHANG Yi-hao, WEI Qing. Inhibition of SNAI2 expression enhances tumor stem cell-like characteristics and multi-drug resistance of hepatoma cells[J]. Chinese Hepatolgy, 2018, 23(11): 981-984.

参考文献

[1] Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol, 2002, 3: 155-166.
[2] Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer, 2007, 7: 415-428.
[3] Bolos V, Peinado H, Perez-Moreno MA, et al. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci, 2003, 116: 499-511.
[4] Gupta PB, Kuperwasser C, Brunet JP, et al. The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nat Genet, 2005, 37: 1047-1054.
[5] Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res, 2002, 62: 1613-1618.
[6] Mancini M, Petta S, Iacobucci I, et al. Zinc-finger transcription factor slug contributes to the survival advantage of chronic myeloid leukemia cells. Cell Signal, 2010, 22:1247-1253.
[7] Chang TH, Tsai MF, Su KY, et al. Slug confers resistance to the epidermal growth factor receptor tyrosine kinase inhibitor. Am J Respir Crit Care Med, 2011, 183: 1071-1079.
[8] Vitali R, Mancini C, Cesi V, et al. Slug (SNAI2) down-regulation by RNA interference facilitates apoptosis and inhibits invasive growth in neuroblastoma preclinical mod- els. Clin Cancer Res, 2008, 14: 4622-4630.
[9] Liu J, Uygur B, Zhang Z, et al. Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression. Prostate, 2010, 70: 1768-1777.
[10] Caramel J, Papadogeorgakis E, Hill L, et al. A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell, 2013, 24: 466-480.
[11] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65: 87-108.
[12] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66: 115-132.
[13] Chiba T, Kita K, Zheng YW, et al. Side population purified from hepa- tocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology, 2006, 44: 240-251.
[14] Ye X, Tam WL, Shibue T, et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature, 2015, 525: 256-260.
[15] Haslehurst AM, Koti M, Dharsee M, et al. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer, 2012, 12: 91.