The microRNA-520a-3p inhibits proliferation,apoptosis and metastasis by targeting MAP3K2 in non-small cell lung cancer

Growing evidence indicates that miR-520a was involved in the complement attack and migration of tumor cells, but nonetheless, the role of miR-520a-3p in non-small cell lung cancer (NSCLC) is not clear. Mitogen-activated protein kinase kinase kinase 2 (MAP3K2) is a kinase belonging to the serine/threonine protein kinase family. To develop potential therapy targeting MAP3K2, we studied the roles of miR-520a-3p in the proliferation, apoptosis and metastasis of NSCLC. The expression levels of miR-520a-3p were quantified in tumor tissues of NSCLC by qRT-PCR, and the mimics and inhibitors were used to verify the function of miR-520a-3p. The cell proliferation was evaluated by MTT assay, and the migration and invasion was evaluated by transwell assay. The athymic mice subcutaneous injection was used to research NSCLC cell tumor formation. The bioinformatics tools and luciferase assay was applied to detect the relationship between miR-520a-3p and its target. Protein levels of miR-520a-3p target was determined by western blot analysis. MiR-520a-3p expression was decreased in the NSCLC tissues compared with their normal counterparts and lower expression of miR-520a-3p in NSCLC tissues was associated with a higher clinical stage, NSCLC metastasis and poor prognosis. Inhibition of expression of miR-520a-3p can reduce in vitro NSCLC cell migration and invasion as well as in vivo metastasis. MAP3K2 mRNA contains a binding site for miR-520a-3p in the 3’UTR. MAP3K2 is one of target of miR-520a-3p. Together, our data demonstrated that miR-520a-3p inhibits proliferation, apoptosis and metastasis in NSCLC by targeting MAP3K2, and miR-520a-3p may be used as a prognosis marker for NSCLC in clinical research.     

BSN-AS2竞争性结合miR-219a-5p影响NSCLC细胞增殖、迁移、侵袭及凋亡

目的:探讨BSN-AS2竞争性结合miR-219a-5p调控非小细胞肺癌（non-small cell lung cancer,NSCLC)细胞增殖、迁移、侵袭和凋亡的机制。方法:qRT-PCR检测BSN-AS2和miR-219a-5p在NSCLC组织和细胞系中的表达;原位杂交FISH检测BSN-AS2和miR-219a-5p的信号强度;双荧光素酶报告基因检验miR-219a-5p 靶向调控BSN-AS2;Transwell、CCK8和Tunel细胞凋亡分别检测BSN-AS2-miR-219a-5p轴对侵袭、迁移、增殖和凋亡的影响;构建NSCLC裸鼠皮下移植瘤模型进行验证BSN-AS2-miR-219a-5p轴的调控作用。结果:BSN-AS2在NSCLC组织和细胞系中高表达,miR-219a-5p为低表达,BSN-AS2竞争性结合miR-219a-5p;siBSN-AS2组抑制NCI-H520细胞侵袭、迁移和增殖,且促进细胞凋亡,而In-miR-219a-5p组促进NCI-H520细胞侵袭、迁移和增殖,抑制细胞凋亡,siBSN-AS2+In-miR-219a-5p组相比siBSN-AS2组促进了NCI-H520细胞侵袭、迁移和增殖,抑制细胞凋亡;BSN-AS2增加体内肿瘤细胞增殖和肿瘤生长,miR-219a-5p则能抑制。结论:BSN-AS2竞争性结合miR-219a-5p促进NSCLC细胞侵袭、迁移和增殖,且抑制凋亡,而干扰BSN-AS2-miR-219a-5p轴可能作为抗NSCLC的新靶点。     

培美曲塞联合舒尼替尼对肝癌细胞生物学行为的影响

目的:探讨培美曲塞联合舒尼替尼对肝癌细胞增殖、细胞周期和细胞凋亡的影响。方法:以培美曲塞和舒尼替尼单药或联合处理肝癌SK-Hep1细胞后,MTT法检测细胞的增殖抑制率,FCM检测细胞的周期变化和凋亡率,Western blot检测蛋白激酶B（AKT）、磷酸化蛋白激酶B（p-AKT）、增殖细胞核抗原（PCNA）、B淋巴细胞瘤-2基因（Bcl-2）和切割型半胱天冬酶3（Cleaved caspase-3）蛋白的表达。结果:培美曲塞和舒尼替尼均能够呈时间-浓度依赖性抑制SK-Hep1细胞增殖,72 h IC50分别为（2.89±0.20）μmol/L和（2.12±0.12）μmol/L（P＜0.05）;培美曲塞和舒尼替尼均能够诱导SK-Hep1细胞凋亡（P＜0.05）;培美曲塞使SK-Hep1细胞周期阻滞于S期,舒尼替尼使细胞周期阻滞于G0/G1期（P＜0.05）;培美曲塞和舒尼替尼均可使p-AKT、PCNA、Bcl-2的表达下降,Cleaved caspase-3表达升高。两药联用使SK-Hep1细胞阻滞在G2/M期,细胞增殖抑制率和细胞凋亡率较单药更加明显,且p-AKT、PCNA、Bcl-2表达下降及Cleaved caspase-3表达升高更为显著（P＜0.05）。结论:培美曲塞联合舒尼替尼可抑制SK-Hep1细胞增殖,并诱导SK-Hep1细胞周期阻滞和凋亡,其作用机制可能与下调p-AKT、PCNA、Bcl-2表达和上调Cleaved caspase-3表达有关。     

Sevoflurane inhibits proliferation, induces apoptosis, and blocks cell cycle progression of lung carcinoma cells

Purpose: Sevoflurane, an inhalational anesthetic, is used extensively during lung cancer surgery. However, the effect of sevoflurane on growth of lung carcinoma cells remains unclear. The purpose of this study is to investigate effects on proliferation, apoptosis, and cell cycling in the A549 human lung adenocarcinoma cell line. Methods: A549 cells were treated with 1.7%, 3.4%, and 5.1 % sevoflurane for 2, 4, and 6 hours. Cell proliferation was evaluated by the MTT assay and colony formation assay. Apoptosis and cell cycle was analyzed by flow cytometry. Expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, Bcl-2, Bax, caspase-3, cyclin A, cyclin B1, and cdc2 was measured by Western blotting. Results: Sgnificant inhibition of cell proliferation and induction of apoptosis were found in A549 cells after sevoflurane treatment. Simultaneously, expression of XIAP and survivin was surpressed, while that of caspase-3 increased significantly, but Bcl-2 and Bax were not altered. Sevoflurane caused cell cycle arrest at the G2/M phase. At the same time, data revealed that cyclin A, cyclin B1, and cdc2 expression was down-regulated after sevoflurane treatment. Conclusion: This study demonstrated that sevoflurane inhibited proliferation, and induced apoptosis in human lung adenocarcinoma A549 cells, associated with down-regulated expression of XIAP and suvivin, and activating caspase-3.     

miR-126-5p靶向Notch2 对结肠癌SW480 细胞增殖、迁移、侵袭和凋亡的影响

目的:探讨miR-126-5p 对结肠癌SW480 细胞增殖、迁移、侵袭和凋亡的影响及其作用机制。方法：用miR-126 mimic和pcDNA Notch2（pc-Notch2）等分别或同时转染结肠癌SW480 细胞,用qPCR法检测miR-126-5p 和Notch2 的表达;荧光素酶报告实验观察miR-126-5p 和Notch2 的靶向关系;CCK-8 法、划痕愈合实验、Transwell 小室法和Annexin V/PI 染色流式细胞术分别检测转染细胞的增殖、迁移、侵袭和凋亡,Western blotting 检测Notch2、增殖细胞核抗原（proliferating cell nuclear antigen, PCNA）、cleaved Caspase-3、MMP-2 和MMP-9 的表达。结果：转染miR-126 mimic 能显著升高SW480 细胞miR-126-5p 的表达水平（P<0.01）和显著抑制SW480 细胞Notch2 的表达（P<0.01）,同时证实Notch2 上存在miR-126-5p 的结合位点。上调miR-126-5p 显著抑制SW480 细胞增殖并降低PCNA的表达水平（P<0.01）、升高细胞凋亡率和cleaved Caspase-9 的表达水平（均P<0.01）,pc-Notch2显著减弱miR-126 mimic 对SW480 细胞增殖和凋亡的调控作用;miR-126 mimic 显著降低SW480 细胞划痕愈合率和穿膜细胞数（均P<0.01）、抑制MMP-2 和MMP-9 的表达（P<0.01）;pc-Notch2 显著减弱miR-126 mimic 对SW480 细胞迁移、侵袭及MMP-2、MMP-9表达的抑制作用（均P<0.01）。结论：miR-126-5p 通过抑制Notch2 表达,降低结肠癌SW480 细胞增殖、迁移和侵袭能力。     

hsa-miR-520h downregulates ABCG2 in pancreatic cancer cells to inhibit migration,invasion, and side populations

Background:

Expression of ABCG2 is normally absent or low in the pancreas, but high in human pancreatic cancer cells. The mechanism by which ABCG2 is altered in human cancers remains unknown.

Methods:

We investigated ABCG2 expression in four pancreatic cancer cell lines, and used three microRNA (miRNA) target prediction programmes, and information from the existing literature to predict and identify hsa-miR-520h as an miRNA that targets ABCG2. The function of this miRNA was investigated by transient transfection of the pancreatic cancer cell line PANC-1 with oligonucleotides that mimic hsa-miR-520h.

Results:

Results showed that both mRNA and protein levels of ABCG2 were reduced, indicating that it was a target of hsa-miR-520h. Introduction of hsa-miR-520h mimics into PANC-1 cells also resulted in inhibition of cell migration and invasion, and reduction of side population cells. Cell proliferation, cell cycle progression and apoptosis were not affected.

Conclusions:

We propose that the effects of hsa-miR-520h may be, at least in part, caused by its regulation of ABCG2. Thus, our findings provide a new insight into the function of miRNA in the regulation of ABCG2 expression in pancreatic cancer. Gene therapy using miRNA mimics may therefore be useful as a pancreatic cancer therapy.     

JAK抑制剂AG490诱导乳腺癌细胞凋亡及对Survivin表达的影响

背景与目的:已有研究证实Survivin在多种乳腺癌中可呈高表达且与肿瘤的恶性程度和患者预后密切相关,但是Survivin在乳腺癌细胞中高表达的相关机制尚有待深入了解。本实验拟研究JAK-STAT信号通路抑制剂AG490在人乳腺癌细胞MDA-MB-231中对Survivin表达以及对肿瘤细胞增殖、凋亡的影响。方法:以MDA-MB-231细胞为研究对象,应用AG490后,用Westernblot检测细胞中P-STAT3、Survivin的蛋白表达变化、RT-PCR检测SurvivinmRNA的变化;用MTT法检测细胞增殖活性的改变;用流式细胞术检测细胞凋亡的情况。结果:AG490使MDA-MB-231细胞中P-STAT3和Survivin的蛋白表达减少,同时细胞的增殖活性降低,凋亡增多。P-STAT3/β-actin用药前为0.74,AG49040μmol/L作用24h后为0.21;Survivin/β-actin用药前为1.09,40μmol/LAG490作用24h后为0.28。40μmol/LAG490作用24h后细胞出现“亚G1”峰,凋亡率为5.62%;AG49040μmol/L,作用48h后细胞凋亡率为28.81%。结论:AG490可诱导MDA-MB-231细胞凋亡、减少Survivin的表达。     

NLRP3炎症小体在槲皮素诱导宫颈癌HeLa细胞凋亡中的作用

目的:探讨槲皮素对人宫颈癌HeLa细胞增殖及凋亡的影响,并探讨其可能的机制。方法:以不同浓度槲皮素（20、40和80 μmol/L）处理HeLa细胞36 h,用噻唑蓝（MTT）法检测细胞增殖情况,流式细胞实验检测细胞凋亡情况,Western blot和实时定量PCR法检测NLRP3炎症小体的表达情况。结果:槲皮素能使HeLa细胞活力降低,差异具有统计意义（P<0.05)。流式细胞结果表明不同浓度槲皮素组均可诱导HeLa细胞凋亡,且能抑制NLRP3炎症小体相关蛋白NLRP3、ASC及Caspase-1的表达。结论:槲皮素能通过下调HeLa细胞中NLRP3炎症小体的表达发挥其促癌细胞凋亡作用。     

DR4基因启动子甲基化对TRAIL诱导肺鳞癌细胞凋亡作用的影响

目的:探讨肺鳞癌中死亡受体4（DR4）不同甲基化状态是否会影响肿瘤坏死因子相关凋亡诱导配体(TRAIL)对肺鳞癌细胞的诱导凋亡作用。方法:采用甲基化特异性PCR（MSP）、RT-PCR和Western blot法检测5-氮-2′-脱氧胞苷（5-Aza-CdR）处理肺鳞癌细胞株（H226、SK-MES-1、H520）前后DR4基因启动子甲基化状态和基因表达情况;MTT法检测细胞增殖抑制率,流式细胞仪检测细胞凋亡率。结果:MSP、RT-PCR和Western blot结果表明H226、SK-MES-1细胞DR4基因呈甲基化状态,其mRNA及蛋白均低表达,H520细胞中DR4基因呈非甲基化状态,其mRNA及蛋白高表达;5-Aza-CdR干预后H226、SK-MES-1细胞DR4基因呈非甲基化状态,其mRNA及蛋白表达较前均显著上调,差异有统计学意义（P＜0.05）,H520仍呈非甲基化状态,其mRNA及蛋白表达量较前无明显差异。同时研究还证实TRAIL对H226、SK-MES-1细胞有不同程度的细胞增殖抑制率和凋亡率,但不敏感,5-Aza-CdR干预后,H226及SK-MES-1细胞对TRAIL的敏感性较前均显著增高（P＜0.05）。结论:5-Aza-CdR可以逆转肺鳞癌中DR4基因启动子甲基化状态,进而增加TRAIL诱导肺鳞癌细胞凋亡的作用。5-Aza-CdR联合TRAIL可能是治疗肺鳞癌的一种新策略。     

Role of TMPRSS4 Modulation in Breast Cancer Cell Proliferation

Background: TMPRSS4 is a novel Type II transmembrane serine protease found at the surface of the cells andis involved in the development and cancer progression. However, TMPRSS4 functions in breast cancer remain poorunderstand. The present study investigated the function of TMPRSS4 in the breast cancer cells and the potentialmechanistic action underling. Materials and Methods: The lentiviral vectors causing TMPRSS4 down-regulation andover-expression were established and transfected in MDA-MB-468 and MCF-7 cells, respectively. By using the CCK-8 assay, cell proliferation was analyzed. Moreover, western blot was used to detect the expression of certain proteinsrelated to cell apoptosis (Bax and Bcl2) signaling pathway and telomere maintenance (POT1, TPP1, and UBE2D3).Cell cycle and cell apoptosis were also analyzed by using the Flow cytometry analysis. TMPRSS4 expression wasdetected at the mRNA level and protein level by performing qPCR and western blot technique, respectively. Results:TMPRSS4 expression is inhibited in stable transfected MDA-MB-468-shTMPRSS4 cells compared to the controlMDA-MB-468-NC and its expression is up-regulated in stable transfected MCF-7-TMPTSS4 compared to its controlMCF-7-NC. Moreover, TMPRSS4 silencing in breast cancer reduces cells proliferation by promoting cell cycle arrestin G2/M phase, cell apoptosis, and telomere maintenance impairment while the TMPRSS4 overexpression increasescells proliferation through cell apoptosis reduction and telomere maintenance reinforcement associated with insignificantchange in cell cycle progression. Conclusion: TMPRSS4 plays important roles in cancer progression and may beconsidered as a good therapeutic target for cancer gene therapy especially breast cancer.     

全反式维甲酸诱导人肝癌细胞HepG2凋亡的初步研究

[目的]研究全反式维甲酸（ATRA）体外诱导人肝癌细胞株HepG2的凋亡及其作用机制。[方法]ATRA处理HepG2细胞。MTT法分析细胞增殖反应;Hoechst染色法检测细胞凋亡情况;Western blot检测细胞中caspase-9、caspase-3和NF-κB蛋白表达情况。[结果]A-TRA可抑制HepG2细胞增殖并诱导细胞凋亡,可上调细胞中caspase-9、caspase-3表达水平（P〈0.05）。[结论]ATRA可抑制HepG2细胞增殖并诱导细胞凋亡,其作用机制可能与cas-pase-9、caspase-3表达上调有关。     

PRUNE2点突变影响前列腺癌DU145细胞增殖、凋亡、侵袭和迁移

背景 与目的:PRUNE2是成神经细胞瘤的一个特异性预后相关基因,在调节成神经细胞瘤的细胞分化、增殖和侵袭方面发挥着重要作用.PRUNE2低表达与前列腺癌的不良预后密切相关.探讨PRUNE2点突变对前列腺癌DU145细胞增殖、凋亡、侵袭和迁移的影响.方法:通过构建PRUNE2基因野生型和突变型过表达的重组载体并将其转染...     

RNAi抑制CAR基因对人肺鳞癌细胞系NCI-H520裸鼠皮下移植瘤生长的影响

  目的  建立RNAi抑制柯萨奇病毒腺病毒受体（coxsackievirus and adenovirus receptor, CAR）基因表达的肺鳞状细胞癌NCI-H520稳定表达细胞系, 将CAR基因沉默的NCI-H520细胞移植于裸鼠体内构建移植瘤模型, 观察裸鼠体内成瘤率及对瘤体生长等方面的影响。  方法  将针对CAR mRNA序列设计的小干扰RNA重组质粒分别以脂质体转染至NCI-H520细胞, 并经G418抗性筛选得到稳定细胞系; 用平板克隆形成实验观察RNAi抑制CAR基因表达对NCI-H520细胞增殖的影响; 通过动态观察瘤体的生长, 进一步验证CAR对肺癌的增殖是否有促进作用。  结果  筛选出抑制CAR基因表达效果最佳的一组shRNA, 并建立了能稳定而有效抑制CAR基因表达的肺鳞癌NCI-H520细胞系。平板克隆形成实验显示, shRNA-2抑制CAR基因表达后NCI-H520细胞的增殖能力有所下降, 但其差异无统计学意义（P>0.05）; 且在肿瘤形成实验中, 实验组瘤重显著低于对照组（P < 0.01）。  结论  裸鼠肺癌移植瘤模型构建成功, 为今后肺癌的研究奠定基础。利用RNAi有效抑制了CAR基因的表达, 并抑制NCI-H520细胞在裸鼠体内瘤体的生长, CAR有望成为肺癌基因治疗的靶点之一。      

MLN4924对紫杉醇耐药的前列腺癌细胞增殖和凋亡的影响

目的:研究MLN4924对紫杉醇耐药的前列腺癌细胞增殖和凋亡的影响,从而为紫杉醇耐药前列腺癌的临床治疗提供新的理论依据。方法:不同浓度的MLN4924作用紫杉醇耐药的前列腺癌细胞PC3-TxR和DU145-TxR 48和72小时后,采用MTS检测细胞活力。Western blot检测凋亡相关蛋白Caspase-3、CDT1、p27以及EMT标志物水平。结果:MLN4924能够显著抑制PC3-TxR和DU145-TxR细胞的增殖,并且具有时间和浓度的依懒性。Western blot结果显示MLN4924作用后显著增加细胞内凋亡相关蛋白Caspase-3、CDT1和p27的表达。结论:MLN4924能够显著抑制紫杉醇耐药的前列腺癌细胞增殖、促进细胞凋亡,其相关机制为MLN4924可通过上调p27蛋白表达促进紫杉醇耐药的前列腺癌细胞凋亡。     

miR-142-5p对人上皮性卵巢癌细胞增殖和凋亡的影响

目的:探讨miR-142-5p靶向PTEN-PI3K/Akt信号调控人上皮性卵巢癌SKOV3细胞增殖和凋亡的具体机制。方法:Real-time PCR检测miR-142-5p在人卵巢癌组织及各卵巢癌细胞系中的表达情况。利用MTT、细胞克隆形成实验观察miR-142-5p对SKOV3细胞增殖活力的影响;Caspase-3活力检测miR-142-5p对SKOV3细胞凋亡情况;信号通路抑制剂处理及Western blot检测miR-142-5p、PTEN与PI3K/Akt信号通路的关系及PI3K/Akt信号下游基因Akt、FOXO1、cyclin D1等的表达情况;Luciferase实验验证miR-142-5p和PTEN 3' UTR的结合。结果:人上皮性卵巢癌组织及其细胞系中miR-142-5p表达显著增加（P<0.05)。与对照组相比,SKOV3细胞转染miR-142-5p mimics后活细胞数量显著增加,增殖能力显著上升,细胞凋亡下降（P<0.05);与之相反的,转染miR-142-5p inhibitor后SKOV3细胞增殖能力下调,凋亡增加。信号通路抑制剂处理显示miR-142-5p过表达激活PI3K/Akt信号通路。Luciferase实验显示miR-142-5p与PTEN 3' UTR直接结合。与对照组相比,miR-142-5p mimics组PTEN表达显著降低,p-Akt蛋白表达则显著上调（P<0.05）,同时过表达PTEN后p-Akt表达则显著降低（P<0.05）。结论:miR-142-5p通过抑制PTEN基因表达活化PI3K/Akt信号通路,促进人上皮性卵巢癌组织及SKOV3细胞增殖存活,抑制细胞凋亡。     

三氧化二砷对人肝癌细胞生长增殖的影响

目的观察三氧化二砷（As2O3）对人BEL7402肝癌细胞株的作用及其机制。方法采用MTF法检测As2O3对BEL7402细胞的生长抑制率;流式细胞仪测定经不同浓度As2O3处理后的BEL7402细胞周期及增殖细胞核抗原（PCNA）变化,同时Annexin V—FITC／PI双染法检测细胞凋亡。结果三氧化二砷可显著抑制BEL7402细胞生长,且剂量-效应关系显著（r=0．9650,P〈0．01）,半数抑制浓度（IC50）为4．93μmol／L;BEL7402经As2O3处理后可发生凋亡。As2O3能显著下调PCNA蛋白表达（P〈0．01）,并使细胞周期阻滞在G2／M期。结论三氧化二砷可有效抑制人肝癌BEL7402细胞生长增殖,其机制可能与诱导细胞凋亡、下调PCNA表达及阻滞细胞周期有关。     

凋亡、PCNA及c-myc表达水平与鼻咽癌放射敏感性的相关性研究

目的:探讨凋亡、增殖细胞核抗原(PCNA)及c-myc之间的相互关系以及它们与放射敏感性的相关关系.方法:搜集31例鼻咽癌患者于放疗前及接受放射剂量1 520CGy后分别从鼻咽部肿物取活检.应用末端脱氧核苷酸转移酶(TdT)介导的脱氧核苷酸缺口末端标记(TUNEL)技术检测肿瘤细胞的凋亡率(AR),应用S-P免疫组化法检测PCNA、c-myc,并将它们与放射敏感性进行相关研究.结果:放疗前c-myc蛋白的表达水平与肿瘤细胞的自发性凋亡呈负相关、与PCNA呈正相关(P＜0.01);放疗后c-myc蛋白的表达水平与放射诱导凋亡呈正相关,与PCNA呈负相关(P＜0.01).肿瘤细胞放射敏感性级别与放疗前PCNA、放疗前凋亡率、放射诱导凋亡、放疗后PCNA下降幅度呈正相关(P＜0.01);而与c-myc无明显相关性(P＞0.05).结论:凋亡及PCNA与鼻咽癌的放射敏感性之间存在密切相关性,而c-mvc对凋亡及细胞增殖有调控作用.     

单克隆抗体PD4诱导人胃癌细胞系MGC-803的凋亡

目的凋亡（Ａｐｏｐｔｏｓｉｓ）是一种区别于坏死的细胞生理性死亡方式。肿瘤发生与凋亡的异常有十分密切的关系。单克隆抗体ＰＤ４能识别胃癌细胞表面的分子量为４００００的分子（Ｐ４０）。本研究是为了观察单抗ＰＤ４是否具有诱导胃癌细胞凋亡的作用。方法我们应用流式细胞术和末端脱氧核苷酸标记及ＤＮＡ电泳法观察单抗ＰＤ４对胃癌细胞ＭＧＣ－８０３增殖周期的影响以及对细胞杀伤作用的方式,并检测了ＭＧＣ－８０３细胞表面Ｆａｓ抗原的表达情况。结果ＰＤ４有阻滞细胞周期、通过诱发凋亡而抑制肿瘤细胞生长的作用,且ＭＧＣ－８０３细胞Ｆａｓ抗原表达为阴性。结论Ｐ４０是一个与细胞凋亡或增殖有关、且不同于Ｆａｓ的肿瘤相关抗原,他的分子克隆有助于抗体诱导细胞凋亡机制的阐明。     

塞来昔布抑制肝癌细胞株增殖及其机制的实验研究

目的:研究特异性环氧化酶-2(COX-2)抑制剂塞来昔布对人肝癌细胞株SMMC-7721是否有抑制增殖、诱导凋亡作用并初步探讨其作用机制。方法:采用四氮唑盐比色法(MTT法)观察不同浓度的塞来昔布作用后细胞增殖活力改变;流式细胞仪检测细胞凋亡百分率及细胞周期变化;免疫组化观察Bcl-2蛋白和Bax蛋白表达情况。结果:MTT法显示随着塞来昔布浓度和作用时间增加,细胞增殖抑制率上升;流式细胞仪测定空白对照组未见明显凋亡峰,塞来昔布组出现凋亡峰,凋亡率随着时间及药物浓度变化而变化,二者呈正相关;免疫组化显示经塞来昔布干预后,凋亡蛋白Bax表达增加,而Bcl-2表达减少,并随时间和药物浓度变化而明显。结论:塞来昔布抑制SMMC-7721细胞增殖,促进SMMC-7721细胞凋亡,并呈剂量和时间依赖性。其作用机制之一可能是通过减少Bcl-2的表达,增加Bax的表达,从而启动细胞凋亡途径。