DLL3沉默抑制小细胞肺癌细胞系H592的增殖和迁移

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摘要目的: 探究DLL3沉默后对小细胞肺癌(small cell lung carcinomas, SCLC)细胞增殖和迁移的影响。方法: 收集陕西省肿瘤医院50例SCLC患者临床信息，免疫组织化学法检测癌组织中DLL3的表达；采用实时荧光定量PCR检测SCLC癌组织和细胞系H592中DLL3的mRNA表达；采用siRNA分别沉默H592细胞中的DLL3和MUC1基因，蛋白质印迹法检测DLL3沉默后细胞内黏蛋白-1（Mucins-1，MUC-1）的表达；分别采用CCK-8、流式细胞仪、Transwell实验检测细胞增殖、凋亡、迁移能力。结果： SCLC组织中DLL3阳性表达率为72%。与癌旁组织比较，癌组织中DLL3 mRNA的表达显著提高(P<0.01)。DLL3在H592细胞中呈高表达（P<0.01）。下调DLL3后，H592细胞增殖、迁移能力减弱，凋亡能力增强；胞内MUC1蛋白表达水平降低。Pearson相关性分析显示DLL3和MUC-1表达水平呈显著正相关（r=0.83, P<0.01）。MUC-1下调后，H592细胞增殖、迁移能力减弱，凋亡能力增强。结论： DLL3和MUC-1在SCLC中表达上调，敲减DLL3和MUC1基因会抑制癌细胞的增殖、迁移，促进凋亡。

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	周菁1
	郭丽2

关键词 ：小细胞肺癌, DLL3, 黏蛋白-1, 增殖, 迁移, 凋亡

Abstract：Objective: To explore the effect of the silencing DLL3 (delta-like ligand 3) on the proliferation and migration of small cell lung cancer(SCLC).Methods: Clinical information of 50 patients with SCLC was collected from Shanxi Province Tumor Hospital, and the expression of DLL3 in cancer tissues was detected by immunohistochemical staining. The mRNA levels of DLL3 in H592 of SCLC cells were detected by real-time fluorescence quantitative PCR. si-RNA was used to silence the expression of DLL3 and MUC-1 genes in H592 cells, respectively. The expression of Mucins-1 (MUC-1) was detected by Western blotting after DLL3 silencing. Cell proliferation, apoptosis and migration were detected by CCK-8, flow cytometry and Transwell assay, respectively. Results: The positive expression of DLL3 in SCLC was 72%. The expression of DLL3 in carcinoma tissues was significantly higher than that in paracancer tissues (P<0.01). DLL3 was highly expressed in H592 cells (P<0.01). After the silencing of DLL3, the proliferation and migration ability of H592 cells were reduced and the apoptotic ability was enhanced. In addition, the intracellular expression level of MUC-1 protein was decreased. Pearson correlation analysis showed that there was a significant positive correlation between the expression levels of DLL3 and MUC-1 (r=0.83, P<0.01). After the silencing of MUC-1, the proliferation and migration ability of H592 cells were reduced and the apoptotic ability was enhanced. Conclusion: DLL3 and MUC-1 were highly expressed in SCLC, and silencing of DLL3 and MUC-1 can inhibit the proliferation and migration of cancer cells and promote apoptosis.

收稿日期: 2020-03-06

基金资助: 陕西省重点研发计划项目（2017SF-080）

通讯作者: 郭丽（通讯作者），硕士，主治医师，E-mail:guoli58727@163.com

作者简介: 周菁（1986—），女，硕士，主治医师，主要从事肿瘤内科相关研究

引用本文:

周菁1，郭丽2. DLL3沉默抑制小细胞肺癌细胞系H592的增殖和迁移[J]. 江苏大学学报:医学版, 2020, 30(04): 330-335. ZHOU Jing1, GUO Li2.

Silencing DLL3 inhibits proliferation and migration of small cell lung cancer cell line H592

. Journal of Jiangsu University(Medicine Edition), 2020, 30(04): 330-335.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2020/V30/I04/330

［1］Oronsky B, Reid TR, Oronsky A, et al. What′s new in SCLC? A Review\[J\]. Neoplasia, 2017, 19(10):842-847.

［2］周毅.小细胞肺癌靶向药物治疗进展\[J\].中外医学研究, 2019, 17(12):186-188.

［3］Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3targeted antibodydrug conjugate eradicates highgrade pulmonary neuroendocrine tumorinitiating cells in vivo\[J\]. Sci Transl Med, 2015, 7(302):302-311.

［4］Tanaka K, Isse K, Fujihira T, et al.Prevalence of Deltalike protein 3 expression in patients with small cell lung cancer\[J\]. Lung Cancer， 2018,115:116-120.

［5］Furuta M, Kikuchi H, Shoji T, et al. DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail\[J\]. Cancer Sci, 2019,110(5):1599-1608.

［6］Rudin CM, Pietanza MC, Bauer TM, et al. Rovalpituzumab tesirine, a DLL3targeted antibodydrug conjugate, in recurrent smallcell lung cancer: a firstinhuman, firstinclass, openlabel, phase 1 study\[J\]. Lancet Oncol, 2017, 18:42-51.

［7］Huang J, Cao D, Sha J, et al. DLL3 is regulated by LIN28B and miR518d5p and regulates cell proliferation, migration and chemotherapy response in advanced small cell lung cancer\[J\]. Biochem Biophys Res Commun, 2019, 514(3):853-860.

［8］Li L, Tang P, Li S, et al. Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy\[J\]. Med Oncol, 2017, 34(10):180-187.

［9］Mizuno Y, Maemura K, Tanaka Y, et al. Expression of deltalike 3 is downregulated by aberrant DNA methylation and histone modification in hepatocellular carcinoma\[J\]. Oncol Rep, 2018, 39(5):2209-2216.

［10］Bouillez A, Rajabi H, Jin C, et al. MUC1C integrates PDL1 induction with repression of immune effectors in nonsmallcell lung cancer\[J\]. Oncogene, 2017, 36(28): 4037-4046.

［11］Cordone I, Masi S, Summa V, et al. Overexpression of syndecan1, MUC1, and putative stem cell markers in breast cancer leptomeningeal metastasis: a cerebrospinal fluid flow cytometry study\[J\]. Breast Cancer Res, 2017, 19(1):46-51.

［12］Ahmad R, Alam M, Hasegawa M, et al. Targeting MUC1C inhibits the AKTS6K1elF4A pathway regulating TIGAR translation in colorectal cancer\[J\]. Molecular Cancer, 2017, 16(1):33-41.

［13］Shukla SK, Purohit V, Mehla K, et al. MUC1 and HIF1α signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer\[J\]. Cancer Cell, 2017, 32(1):71-87.

［14］Endo S, Nishimura N, Kawano Y, et al. MUC1/KL6 expression confers an aggressive phenotype upon myeloma cells\[J\]. Biochem Biophys Res Commun, 2018, 507(1-4):246-252.