CN107130021B - Ccat1长链非编码rna及其小分子抑制剂在肝细胞癌治疗方面的应用 - Google Patents

Ccat1长链非编码rna及其小分子抑制剂在肝细胞癌治疗方面的应用 Download PDF

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CN107130021B
CN107130021B CN201710306904.0A CN201710306904A CN107130021B CN 107130021 B CN107130021 B CN 107130021B CN 201710306904 A CN201710306904 A CN 201710306904A CN 107130021 B CN107130021 B CN 107130021B
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王莉
王旻
李岩
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Zhongyu Medical Laboratory (Guangzhou) Co., Ltd
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Abstract

本发明公开了CCAT1长链非编码RNA及其小分子抑制剂在肝细胞癌治疗方面的应用。本发明发现，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ可以显著抑制肝癌Hep3b细胞中LncRNA CCAT1的表达，从而显著抑制肝癌Hep3b细胞的体外增殖和体内成瘤能力。吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ及其他LncRNA CCAT1的抑制剂可以用于开发制备成治疗肝癌的药物。本发明具有突出的实质性特点和显著的进步。

Description

CCAT1长链非编码RNA及其小分子抑制剂在肝细胞癌治疗方面 的应用
技术领域
本发明属于基因治疗领域，涉及基因靶标及其抑制剂的应用，具体涉及LncRNACCAT1及其小分子抑制剂在肝细胞癌治疗方面的应用。
背景技术
肝细胞癌是全世界最常见的恶性肿瘤之一，每年约有60万患者被诊断出患有肝细胞癌。目前，对于肝细胞癌的治疗主要是手术切除、肝脏移植、放化疗等，但仅有20％的患者能够被治疗。我国肝细胞癌年死亡率占肿瘤死亡率的第2位。肝细胞癌的病因及发病机制尚未确定，因此，寻找新的肝细胞癌的治疗靶点和药物是研究重点。
非编码RNA是指不编码蛋白质的RNA，其中包括rRNA、tRNA、snRNA、snoRNA、miRNA及长链非编码RNA(Lnc RNA)。Lnc RNA是一类长度大于200碱基的RNA分子，由于缺少有效的开放式阅读框不编码蛋白，但具备复杂的生物学功能并在各种生物过程中发挥重要的作用，如染色质修饰、X染色体的失活、参与基因转录、翻译以及到蛋白活动调控等，其变异和调节能够导致包括肿瘤在内的多重疾病。异常表达的Lnc RNA可通过不同途径和不同作用机制参与肿瘤的发生、发展、侵袭和转移的各个阶段，是肿瘤进展的关键因素。近年来研究表明异常表达的Lnc RNA通过多重途径参与了肿瘤细胞的凋亡、増殖、侵袭与转移等调控，与肝癌等肿瘤的发生与转移具有密切的关系。其中，Lnc RNA CCAT1是最早在结肠癌中发现的一个与结肠癌发生发展有关的Lnc RNA。
发明内容
本发明目的在于提供LncRNA CCAT1及其小分子抑制剂在肝细胞癌治疗方面的应用。
实现本发明上述目的技术方案如下：
LncRNA CCAT1作为药物靶标在制备治疗肝癌药物方面的应用。
LncRNA CCAT1抑制剂在制备治疗肝癌药物方面的应用。
优选地，所述抑制剂为具有如下结构通式的吡咯并嘧啶酯类小分子化合物：
Figure BDA0001285981190000011
其中，R为烷基。
优选地，所述抑制剂选自如下结构的化合物：
Figure BDA0001285981190000021
一种药物组合物，含有上述任一所述的抑制剂。
上述药物组合物在制备治疗肝癌药物方面的应用。
本发明的突出优点：
本发明发现，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ可以显著抑制肝癌Hep3b细胞中LncRNA CCAT1的表达，从而显著抑制肝癌Hep3b细胞的体外增殖和体内成瘤能力。吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ及其他LncRNA CCAT1的抑制剂可以用于开发制备成治疗肝癌的药物。
附图说明
图1为各组Hep3b细胞LncRNA CCAT1相对表达水平；
图2为各组Hep3b细胞相对增殖活力(％)；
图3为各组体内抑瘤率(％)；
图4为各组移植瘤LncRNA CCAT1相对表达水平。
具体实施方式
下面就结合实施例具体介绍本发明的实质性内容，由于篇幅原因，实验过程的描述无法做到非常详细，凡是实验中未详细描述的部分均为本领域技术人员熟知的常规操作。
一、实验材料
人肝癌细胞系Hep3b细胞为本公司长期冻存。SPF级4周龄雄性裸鼠购于上海斯莱克实验动物公司。吡咯并嘧啶酯Ⅰ、Ⅱ、Ⅲ由本公司合成部按照文献方法合成，结构经核磁确证。用DMSO溶解制成1mg/mL的母液，根据需要稀释至不同浓度。胎牛血清购自杭州四季青生物工程和材料研究所，DMEM培养基购自Gibco公司。
二、实验方法
1、细胞培养和分组
复苏培养人肝癌细胞系Hep3b细胞。以含10％胎牛血清的DMEM培养基(含双抗)常规培养于37℃、5％CO2和相对湿度95％的恒温培养箱中。细胞经过消化传代，取对数生长期的细胞进行培养及实验。实验前用台盼蓝拒染法确保所用细胞拒染率在95％以上。
给药组分组和给药浓度如下：
吡咯并嘧啶酯Ⅰ组：培养液中含终浓度为5μM、20μM的吡咯并嘧啶酯Ⅰ；
吡咯并嘧啶酯Ⅱ组：培养液中含终浓度为5μM、20μM的吡咯并嘧啶酯Ⅱ；
吡咯并嘧啶酯Ⅲ组：培养液中含终浓度为5μM、20μM的吡咯并嘧啶酯Ⅲ。
2、RNA提取和RT-PCR检测CCAT1相对表达水平
将Hep3b细胞消化计数后加入6孔板，细胞密度为2.5×105/mL，细胞贴壁后，加入吡咯并嘧啶酯5μM、20μM培养24h，收集细胞，测定CCAT1相对表达水平。另设置对照组，对照组不添加吡咯并嘧啶酯。使用TRIzol试剂(Invitrogen公司)提取总RNA。使用PrimeScriptRT试剂盒(TaKaRa公司)在标准条件下的随机引物，将总RNA(500ng)反转录为10μL的最终体积。CCAT1表达水平的检测按照STBR Premix Ex Taq(TaKaRa公司)的使用说明进行。通过2-ΔΔCt方法，根据内参GAPDH含量计算CCAT1的相对表达水平。
LncRNA CCAT1和GAPDH的RT-PCR引物如下：
CCAT1上游引物：5’-CCAATTGAACCGAGCCTTGT-3’；
CCAT1下游引物：5’-TCGTGAGCGTTTTCGCAATG-3’；
GAPDH上游引物：5’-TCCTCTGACTTCAACAGCGACAC-3’；
GAPDH下游引物：5’-TCTCTCTTCCTCTTGTGCTCTTGC-3’。
3、吡咯并嘧啶酯体外对肝癌细胞增殖能力的影响
将Hep3b细胞消化计数后加入96孔板，细胞密度为1×106/mL，每孔100μL，细胞贴壁后，加入吡咯并嘧啶酯5μM、20μM培养48h向各孔中分别加入10μL CCK-8试剂，振荡细胞板后继续培养1h，酶标仪检测吸光度值A(测定波长450nm，参比波长655nm)，计算各组增殖抑制率，该实验重复3次。对照组不添加吡咯并嘧啶酯。
增殖抑制率(％)＝(1-A给药组/A对照组)×100％。
4、吡咯并嘧啶酯体内对肝细胞癌移植瘤的影响
40只裸鼠饲养于SPF环境下，随机分为吡咯并嘧啶酯Ⅰ组、吡咯并嘧啶酯Ⅱ组、吡咯并嘧啶酯Ⅲ组和正常对照组，每组10只。适应性驯养1周后，在裸鼠腋窝皮下接种0.1mL的Hep3b细胞悬液(含5×106个对数生长期的细胞)。当肿瘤体积生长至100mm3左右(约10d)的时候开始分组腹腔给药吡咯并嘧啶酯，给药剂量为10mg/(kg·d)。正常对照组给与等体积的生理盐水。连续给药14天后，按如下公式计算抑瘤率(％)。
抑瘤率(％)＝(1-负载外泌体组肿瘤体积/对照组肿瘤体积)×100％。
5、测定移植瘤中CCAT1相对表达水平
液氮磨肿瘤组织提取RNA，取100mg组织加入1mL Trizol，提取总RNA。使用PrimeScript RT试剂盒(TaKaRa公司)在标准条件下的随机引物，将总RNA(500ng)反转录为10μL的最终体积。CCAT1表达水平的检测按照STBR Premix Ex Taq(TaKaRa公司)的使用说明进行。通过2-ΔΔCt方法，根据内参GAPDH含量计算CCAT1的相对表达水平。
LncRNA CCAT1和GAPDH的RT-PCR引物如下：
CCAT1上游引物：5’-CCAATTGAACCGAGCCTTGT-3’；
CCAT1下游引物：5’-TCGTGAGCGTTTTCGCAATG-3’；
GAPDH上游引物：5’-TCCTCTGACTTCAACAGCGACAC-3’；
GAPDH下游引物：5’-TCTCTCTTCCTCTTGTGCTCTTGC-3’。
6、统计学方法
采用SPSS16.0统计软件进行数据分析，以P<0.05为差异有统计学意义。
三、实验结果
1、吡咯并嘧啶酯对Hep3b细胞中LncRNA CCAT1相对表达水平的影响
与对照组相比，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ给药组Hep3b细胞LncRNA CCAT1相对表达水平均显著降低(P＜0.05)，且高浓度组(20μM)比低浓度组(5μM)Hep3b细胞LncRNA CCAT1相对表达水平降低更为显著。表1和图1为各组Hep3b细胞LncRNACCAT1相对表达水平比较。
表1 各组Hep3b细胞LncRNA CCAT1相对表达水平
Figure BDA0001285981190000041
2、吡咯并嘧啶酯体外对Hep3b细胞增殖能力的影响
与对照组相比，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ给药组Hep3b细胞的增殖活力显著降低(P＜0.05)，且高浓度组(20μM)比低浓度组(5μM)Hep3b细胞增殖活力降低更为显著。表2和图2为各组Hep3b细胞相对增殖活力比较。
表2 各组Hep3b细胞相对增殖活力(％)
Figure BDA0001285981190000051
3、吡咯并嘧啶酯体内对肝细胞癌移植瘤的影响
与对照组相比，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ给药组移植瘤体积明显较小(P＜0.05)，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ显示出明显的体内抑瘤作用。表3和图3为各组体内抑瘤率(％)。
表3 各组体内抑瘤率(％)
吡咯并嘧啶酯Ⅰ组 吡咯并嘧啶酯Ⅱ组 吡咯并嘧啶酯Ⅲ组
抑瘤率(％) 52 57 55
4、吡咯并嘧啶酯对移植瘤LncRNA CCAT1相对表达水平的影响
与对照组相比，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ给药组移植瘤LncRNA CCAT1相对表达水平显著降低(P＜0.05)。
表4和图4为各组移植瘤LncRNA CCAT1相对表达水平比较。
表4 各组移植瘤LncRNA CCAT1相对表达水平
组别 CCAT1/GAPDH
吡咯并嘧啶酯Ⅰ组 0.56
吡咯并嘧啶酯Ⅱ组 0.49
吡咯并嘧啶酯Ⅲ组 0.61
对照组 1.15
上述实验可以发现，吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ可以显著抑制肝癌Hep3b细胞中LncRNA CCAT1的表达，从而显著抑制肝癌Hep3b细胞的体外增殖和体内成瘤能力。吡咯并嘧啶酯Ⅰ、吡咯并嘧啶酯Ⅱ和吡咯并嘧啶酯Ⅲ及其他LncRNA CCAT1的抑制剂可以用于开发制备成治疗肝癌的药物。
上述实施例是对本发明实质性内容的体现，用于更好地解释本发明，但本领域技术人员应当知晓，不应将本发明的保护范围局限于上述具体的实施例。

Claims (1)

1.一种LncRNA CCAT1抑制剂在制备治疗肝癌药物方面的应用，其特征在于，所述LncRNA CCAT1抑制剂选自如下结构的化合物：
Figure FDA0002440058120000011
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016094420A1 (en) * 2014-12-08 2016-06-16 The Regents Of The University Of Michigan Non-coding rnas and uses thereof
CN105899672A (zh) * 2013-09-05 2016-08-24 杰克逊实验室 用于rna-染色质相互作用分析的组合物及其用途

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105899672A (zh) * 2013-09-05 2016-08-24 杰克逊实验室 用于rna-染色质相互作用分析的组合物及其用途
WO2016094420A1 (en) * 2014-12-08 2016-06-16 The Regents Of The University Of Michigan Non-coding rnas and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CCAT1: a pivotal oncogenic long non-coding RNA in human cancers;Xin, Yu等;《CELL PROLIFERATION》;20160630;第49卷(第3期);第255-260页 *

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