Inhibitory effect of sulindac against chemically induced primary colonic tumours by N methyl N nitrosourea in mice

AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.

Growth inhibition and apoptosis induction Sulindac on Human gastric cancer cells

AIM: To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC) cells. METHODS: The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG(2) and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX-2) and Bcl-2 were detected by Western dot blotting. RESULTS: Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG(2) and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG(2) cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24 hours incubation with sulindac at 2mmol x L(-1) and 4mmol x L(-1), the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG(2) cells but not in MKN28 cells. CONCLUSION: Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2 and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater than that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.

Sulindac induces apoptosis and protects against colon carcinoma in mice

AIM: To study the effect of sulindac on colon cancer induction in mice. METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynudeobdyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena. RESULTS: Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%, and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H=33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet. CONCLUSION: Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.

Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion

ATP-binding cassette（ABC） transporters ABCC1（MRP1）,ABCB1（P-gp）,and ABCG2（BCRP） contribute to chemotherapy failure.The primary goals of this study were to characterize the efficacy and mechanism of the nonsteroidal anti-inflammatory drug（NSAID）,sulindac sulfide,to reverse ABCC1 mediated resistance to chemotherapeutic drugs and to determine if sulindac sulfide can influence sensitivity to chemotherapeutic drugs independently of drug efflux.Cytotoxicity assays were performed to measure resistance of ABC-expressing cell lines to doxorubicin and other chemotherapeutic drugs.NSAIDs were tested for the ability to restore sensitivity to resistance selected tumor cell lines,as well as a large panel of standard tumor cell lines.Other experiments characterized the mechanism by which sulindac sulfide inhibits ABCC1 substrate and co-substrate（GSH） transport in isolated membrane vesicles and intact cells.Selective reversal of multi-drug resistance（MDR）,decreased efflux of doxorubicin,and fluorescent substrates were demonstrated by sulindac sulfide and a related NSAID,indomethacin,in resistance selected and engineered cell lines expressing ABCC 1,but not ABCB 1 or ABCG2.Sulindac sulfide also inhibited transport of leukotriene C_4 into membrane vesicles.Sulindac sulfide enhanced the sensitivity to doxorubicin in 24 of 47 tumor cell lines,including all melanoma lines tested（7-7）.Sulindac sulfide also decreased intracellular GSH in ABCC1 expressing cells,while the glutathione synthesis inhibitor,BSO,selectively increased sensitivity to sulindac sulfide induced cytotoxicity.Sulindac sulfide potently and selectively reverses ABCC1-mediated MDR at clinically achievable concentrations.ABCC1 expressing tumors may be highly sensitive to the direct cytotoxicity of sulindac sulfide,and in combination with chemotherapeutic drugs that induce oxidative stress.

Sulindac对人肝癌细胞HepG2增殖及β-catenin表达的影响

目的观察Sulindac对人肝癌细胞HepG2增殖、凋亡及β-catenin蛋白表达的影响,探讨Sulindac抗肝癌的可能机制。方法不同浓度的Sulindac作用HepG2细胞后,采用MTT实验检测细胞增殖抑制作用;采用Hoechst33258染色法检测Sulindac对HepG2细胞凋亡的影响;利用RT-PCR及Western blotting检测HepG2细胞在Sulindac作用后Wint通路中β-catenin的表达变化。结果 Sulindac对人肝癌细胞HepG2有增殖抑制作用,且呈剂量时间依赖关系;Hoechst33258结果显示,Sulindac作用24 h后HepG2细胞凋亡数目明显增多;随着Sulindac浓度的增加,β-catenin mRNA及蛋白表达量逐渐下降。结论 Sulindac能够抑制人肝癌细胞HepG2增殖,通过阻断Wnt信号传导通路,降低β-catenin表达,诱导人肝癌细胞HepG2的凋亡。

Sulindac for stroke treatment: neuroprotective mechanism and therapy

Sulindac, a widely used nonsteroidal anti-inflammatory drug （NSAID） is a prodrug that is reduced by methionine sulfoxide reductase to its active form as an inhibitor of cyclooxygenase 1 and 2. The drug has been shown to elicit tissue protection by processes that may include at least three functions： antioxidant, preconditioning and anti-inflammatory. Sulindac demonstrates neuroprotection that involves inhibition of mitochondrial calcium overload or a decrease in protein oxidation.

Cyclin G2,a novel target of sulindac to inhibit cell cycle progression in colorectal cancer

Sulindac has shown significant clinical benefit in preventing colorectal cancer pro-gression,but its mechanism of action has not been fully elucidated.We have found that sulin-dac sulfide(SS)is able to inhibit cell cycle progression in human colorectal cancer cells,particularly through G1 arrest.To understand the underlying mechanisms of sulindac inhibitory activity,we have demonstrated that Cyclin G2 up-regulation upon SS treatment can substan-tially delay cell cycle progression by enhancing the transcriptional activity of FOXO3a in human colorectal tumor cells.MiR-182,an oncogenic microRNA known to inhibit FOXO3a gene expres-sion,is also involved in the suppressive effect of SS on cell cycle progression.This process be-gins with the down-regulation of miR-182,followed by the enhancement of FOXO3a transcriptional activity and the up-regulation of Cyclin G2.To further determine the clinical utility of this axis,we analyzed the expression of miR-182/FOXO3a/Cyclin G2 in human colo-rectal tumor samples.Our results show not only that there are significant dfferences in miR-182/FOXO3a/Cyclin G2 between tumors and normal tissues,but also that the synergetic effect of miR-182 and FOXO3a is associated with predicting tumor progression.Our study dem-onstrates a novel mechanistic axis consisting of miR-182/FOXO3a/Cyclin G2 that mediates su-lindac inhibition of cell cycle progression.

Sulindac derivative-induced apoptosis in a human umbilical vein endothelial cell line ECV304

Objective To investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro Methods The proliferation profile of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method Cell cycle distribution, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, respectively Results MTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose dependent; the IC 50 was 200 μmol/L FCM showed that the sulfide changed cell cycle distribution The cell cycle distribution was as follows: G 1 phase (control group 77 74%±1 58%; sulfone group 75 63%±2 12%; sulfide group 46 12%±1 60%); S phase (control group 13 64%±1 22%; sulfone group 16 40±2 30%; sulfide group 27 26%±2 08%); G 2 M phase (control group 8 61%±0 67%; sulfone group 7 98%±0 49%; sulfide group 26 62%±3 54%) The apoptosis rates in the control group, sulfone group and sulfide group were 6 08%±3 39%, 4 81%±2 14% and 51 90%±5 67%, respectively Sulfide reduced the proportion of G 1 phase, increased the proportion of S phase, G 2 M phase and the apoptosis rate significantly ( P <0 01, vs control) In the sulfide treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells Apoptotic bodies were observed Sulfone showed no effect on cell proliferation, cell cycle distribution or cell morphology Conclusions Sulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution and arrest cells in G 2 M phase where apoptosis may be induced Sulfone has no such effects on this cell line

舒林酸和吲哚美辛对人血管内皮细胞ECV304的生长抑制作用

目的 体外研究非甾体类消炎药对人血管内皮细胞的生长抑制作用。方法 采用舒林酸和吲哚美辛作用于人脐静脉内皮细胞株ECV30 4 ,并设置不同的作用浓度和作用时间 ,以体外药物敏感实验 (MTT)检测舒林酸和吲哚美辛在不同浓度及作用时间下对ECV30 4细胞的增殖抑制效应 ;以流式细胞仪技术和Hoechst332 5 8荧光染色检测药物作用后细胞有无凋亡改变及其形态学变化。结果 舒林酸和吲哚美辛在体外对ECV30 4细胞均有显著的生长抑制作用 ,并且具有时间和剂量依赖性 ,舒林酸能显著诱导ECV30 4细胞产生凋亡。结论 舒林酸和吲哚美辛在体外具有良好的抑制人脐静脉内皮细胞株ECV30 4生长的作用 ,非甾体类消炎药能够诱导血管内皮细胞产生凋亡而抑制其生长 ,同时也可能存在其他的作用机制。

舒林酸治疗家族性腺瘤性息肉病患者结直肠腺瘤的长期疗效观察

目的观察长期服用舒林酸对家族性腺瘤性息肉病(FAP)患者结直肠腺瘤消退的作用以及对结直肠中残存腺瘤组织病理学表现的影响。方法根据家族史和结肠镜检确诊FAP患者,经患者同意后每天口服舒林酸400mg。患者定期复查结肠镜评价疗效,对残存息肉进行活检病理组织学检查。结果18例FAP患者接受舒林酸长期治疗,平均维持治疗时间为(65.3±31.6)月。最后一次复查时息肉数目均较治疗前明显减少(P=0.02)。舒林酸治疗前FAP患者结直肠腺瘤活检标本中,管状腺瘤占活检腺瘤总数的86.5%,绒毛管状腺瘤占13.0%,绒毛状腺瘤占0.5%。异型程度为Ⅰ级、Ⅱ级、Ⅲ级的腺瘤分别占40.0%、43.5%和11.5%。治疗后获得的腺瘤标本中,管状腺瘤占活检腺瘤总数的97.7%,绒毛管状腺瘤占2.3%。与治疗前相比差异有统计学意义(P<0.01)。异型程度为Ⅰ级、Ⅱ级、Ⅲ级的腺瘤分别占48.9%、48.1%和3.0%,与治疗前相比异型程度显著下降(P<0.01)。但是,有1名患者自行将舒林酸减至每天100mg,一年后发生结肠癌。结论舒林酸长期维持治疗可使家族性腺瘤性息肉病患者结直肠腺瘤保持长期显著消退状态,结直肠残存腺瘤异型程度下降,绒毛管状腺瘤减少。但是腺瘤消退与维持剂量有关,剂量过小无效,而且舒林酸对腺瘤的消退作用是不完全的,患者仍需定期复查肠镜,早期发现结直肠癌。

舒林酸抑制人胃腺癌细胞增殖及诱导凋亡

目的在体外对舒林酸抗人胃腺癌细胞增殖和凋亡诱导作用及其机制进行初步研究.方法采用人胃腺癌细胞株 MKN45,MKN28作为研究对象.体外药物敏感试验(MTT)检测不同浓度和作用时间的舒林酸对细胞的增殖抑制效应;分别用 Hoechst33258细胞核荧光染色、透射电镜和 DNA 琼脂糖凝胶电泳观察舒林酸诱导的细胞凋亡改变;应用 Western 斑点免疫印迹法观察经舒林酸2rnmol·L^(-1)和4mmol·L^(-1)作用24h 后细胞内环氧化酶-2(COX-2)和凋亡抑制蛋白 Bcl-2表达程度的变化.结果舒林酸对人胃腺癌细胞 MKN45,MKN28的杀伤率随着剂量的增大和作用时间的延长而增加,舒林酸对不同类型的细胞杀伤率不同.舒林酸能够诱导人胃腺癌细胞 MKN45,MKN28产生凋亡,凋亡诱导作用的强弱同样具有时间和剂量依赖性,而且对不同类型胃癌细胞的凋亡诱导效应有显著差异.经舒林酸2 mmol·L^(-1)和4mmol·L^(-1)作用24h 后,MKN45细胞内 COX-2和 Bcl-2蛋白比未经舒林酸作用的细胞表达明显减少,而 MKN28细胞内 COX-2和 Bcl-2蛋白的表达未出现明显变化.结论舒林酸在体外对人胃腺癌细胞株 MKN45和 MKN28有良好的增殖抑制作用,诱导凋亡是其抑制胃癌细胞增殖的重要作用机制.舒林酸对人胃腺癌细胞的抑制和凋亡诱导作用与其抑制细胞内环氧化酶-2,并进而抑制 Bcl-2的表达有关,并可能与胃癌细胞的分化状态有关.

舒林酸的合成工艺研究

非甾体抗炎药舒林酸在治疗结肠性息肉和抑制早期癌症方面有良好效果。今介绍舒林酸的改进合成工艺:以对氟氯苄为起始原料,与甲基丙二酸二乙酯缩合,碱性水解,脱羧,SOCl2酰氯化,分子内Friedel-Crafts酰基化、与氰乙酸缩合,水解,与对甲硫基苯甲醛缩合以及氧化反应,制得舒林酸。反应过程中,考察了反应温度,催化剂用量,投料比等对收率的影响,得出最佳反应条件。脱羧反应,温度控制在130～140℃;Friedel-Crafts反应,催化剂无水AlCl3与2-(4-氟苯基)-2-甲基丙二酸的质量比为0.6:1;6-氟-2-甲基茚酮与氰乙酸的缩合反应,催化剂乙酸铵与6-氟-2-甲基茚酮的质量比为0.1:1;5-氟-2-甲基-3-茚乙酸与对甲硫基苯甲醛的缩合反应,5-氟-2-甲基-3-茚乙酸、对甲硫基苯甲醛、甲醇钠的摩尔比为1:1:2.5～4.0;氧化反应,5-氟-2-甲基-1-(4-甲硫基苯亚甲基)-3-茚乙酸与H2O2的质量比为1:0.15。中间体和产品的纯度和结构经气相色谱,气质联用仪,红外光谱及核磁共振仪确定。

舒林酸对结肠癌细胞SW480FasL蛋白表达及诱导淋巴细胞凋亡的影响

目的在体外通过细胞培养,探讨舒林酸对结、直肠癌发生、发展的化学预防机制。方法应用Western blot法检测舒林酸作用前后SW480细胞FasL蛋白表达的变化;应用流式细胞术检测舒林酸作用前后SW480细胞诱导淋巴细胞凋亡率的变化。结果舒林酸处理后较处理前SW480细胞FasL蛋白表达明显降低,而且FasL蛋白表达随舒林酸作用浓度增加显著降低;随舒林酸作用浓度升高,SW480细胞诱导淋巴细胞凋亡率明显降低,不同浓度组比较均有显著性差异(P<0.01)。结论舒林酸降低结肠癌SW480细胞FasL蛋白表达,使SW480细胞诱导Jurkat细胞凋亡率降低,可能是其对结、直肠癌发生、发展的化学预防机制。

保健酒中舒林酸免疫学检测方法的建立

舒林酸是常用非甾体抗炎药物,近期常发现不法生产者在保健酒中添加舒林酸增加治疗效果,这种现象对消费者健康构成威胁。为了建立快速检测舒林酸的免疫学方法,本文以活泼酯法将舒林酸分别连接到BSA制备免疫抗原,连接到OVA上制备检测抗原。用免疫抗原免疫家兔制备多克隆抗体,配合检测抗原经条件优化建立竞争抑制酶联免疫吸附检测方法。实验结果表明,检测体系IC50值为18.1 ng/mL,最低检测限为3.5 ng/mL,检测保健酒中舒林酸加标回收率在82.1-94.2%,变异系数小于7.6%。与8种相关药物交叉反应率都小于0.05%。与用ELISA方法与HPLC检测市售保健酒,2例阳性和28例阴性结果全部吻合。因此,本文所建立的舒林酸免疫学检测方法具有灵敏度高和特异性强的特点,能够满足保健酒中快速筛选舒林酸的需要。

舒林酸在防治小鼠大肠癌中对p53和p21^(WAF1)影响的初步研究

目的:细胞凋亡受到抑制与大肠癌的发生有密切联系。近年来发现长期应用舒林酸等非甾体抗炎药(NSAID)对人的结肠癌、直肠癌和癌前病变的发生发展有预防作用。本实验试图通过对凋亡调控基因的观察,初步探讨舒林酸抗肿瘤作用可能存在的分子机制。方法:利用二甲肼诱发的小鼠实验性大肠癌动物模型,采用TUNEL原位杂交和免疫组化染色的方法,分别标记细胞凋亡、p53、p21阳性细胞,多阶段地动态观察诱癌过程中蛋白表达的变化和舒林酸对它们的影响。结果:p53蛋白表达阳性细胞密度随着病变加重而增加,p21阳性细胞密度升高趋势不明显,预防组、治疗组的p53和p21阳性率都与模型组无显著性差异(P>0.05)。预防组和治疗组中p53低于模型组(P<0.05),p21表达则高于模型组(P<0.05)。结论:舒林酸可以通过上调p21的表达,抑制突变型p53的表达,诱导细胞凋亡,抑制肿瘤形成和进展。

光谱法研究吲哚美辛,舒林酸及其金属配合物与牛血清蛋白的相互作用

以曙红Y(Eosin Y)为探针,采用竞争结合法考查了非甾体抗炎药吲哚美辛和舒林酸及其相关的金属配合物与BSA的结合。在中性环境中,曙红Y的吸收光谱随着BSA的加入发生明显变化,结果表明,曙红Y与BSA之间的结合以静电作用为主,两者之间可能发生电子转移。曙红Y与BSA结合后,抗炎药吲哚美辛,舒林酸的加入可以破坏这种结合,曙红Y部分游离出来,其吸收值恢复,说明药物可以同样的方式结合到BSA上,抢占曙红Y在BSA上的结合位点。将药物转化为金属配合物后,与血清蛋白的亲和程度更强,铜(Ⅱ)的配合物最为突出,推测将非甾体抗炎药转化为铜配合物后,有更好的药理活性。

舒林酸食道支架放疗联合治疗食道癌48例分析

目的 :探讨一种既能改善食道癌性狭窄所致的吞咽困难 ,又能抑制肿瘤生长的治疗手段。方法 :在 1 996～ 1 999年期间 ,采用舒林酸 (sulindac)、支架、放疗 2 6例患者 ,与同期间硒宝康、支架、放疗 2 2例患者进行对照观察 ,比较两组的吞咽困难积分改善情况和 3年存活率。结果 :舒林酸组与硒宝康组吞咽困难积分无显著差异 (P >0 .0 5) ,3年生存率分别为 46 .5 %和 2 2 .7%。P <0 .0 5有显著差异。结论 :舒林酸、支架、放疗对晚期食管癌治疗具有较多好疗效 ,既改善了吞咽困难 ,又控制肿瘤细胞生长 。

舒林酸对人γδT细胞的作用研究

目的:探讨舒林酸在预防消化道肿瘤中对人γδT细胞的影响。方法:异戊烯焦磷酸法体外扩增人外周血γδT细胞。不同浓度的舒林酸诱导γδT细胞和胃腺癌细胞(SGC-7901),流式细胞术检测培养前后的γδT细胞表面标记及检测舒林酸诱导的γδT细胞和SGC-7901细胞凋亡百分率。乳酸脱氢酶法测定γδT细胞的杀伤活性。结果:γδT细胞培养10天时从扩增前4.21%增加到70.35%,CD44达94.0%。舒林酸在100%mol/L时对γδT细胞的生长抑制率达42.1%,明显高于对SGC-7901抑制率(7.4%)。γδT细胞和胃腺癌细胞SGC-7901细胞经不同浓度的舒林酸诱导24h后杀伤SGC-7901细胞作用在12.5μmol/L时最强。舒林酸浓度在100%mol/L时对γδT细胞作用24h的凋亡率(52.71%)显著高于SGC-7901细胞(7.88%)。结论:舒林酸在临床常规使用的药物浓度时可增强γδT细胞杀伤瘤细胞作用,超过这一浓度可明显抑制γδT细胞的增殖能力和杀伤活性,而对胃癌细胞株抑制作用不明显。这一结果为临床非甾体类药物预防消化道肿瘤的用量提供了实验依据。

舒林酸对结肠癌变中Fas和FasL蛋白表达影响的初步研究

目的 :探讨舒林酸诱导肿瘤细胞凋亡可能存在的分子机制。方法 :利用二甲肼诱发的小鼠实验性大肠癌动物模型 ,采用免疫组织化学染色的方法 ,分别标记Fas及FasL阳性细胞 ,观察诱癌过程中Fas和FasL蛋白表达细胞的分布与密度变化和舒林酸对它们的影响。结果 :Fas和FasL的表达阳性产物主要位于细胞浆 ,阳性细胞均位于大肠黏膜表层上皮中 ,呈簇状分布 ,舒林酸预防组和治疗组Fas和FasL表达量与模型组比较差别有统计学意义 (P<0.05)。结论 :舒林酸可以上调Fas和FasL的表达 ,诱导细胞凋亡 ,抑制肿瘤形成和发展。

舒林酸对HBV X基因转染的肝癌细胞Wnt信号通路的影响

目的探讨非甾体类抗炎药舒林酸(Sulindac)对HBV X基因转染的人肝癌SMMC7721细胞系Wnt信号通路的影响。方法用脂质体转染方法将HBx真核表达载体pcDNA3-X瞬时转染SMMC7721细胞(SMMC7721/HBx),以转染空载体pcDNA3的SMMC7721细胞组(SMMC7721/pcDNA3)及未转染质粒的SMMC7721细胞组(SMMC7721)为对照,于转染后72 h用RT-PCR和Western blot检测HBx的表达;并以各种浓度的舒林酸于瞬时转染后24 h干预SMMC7721/HBx组和SMMC7721/pcDNA3组至72 h,Western blot和免疫细胞化学检测β-catenin的表达,Western blot检测cyclinD1的表达。结果RT-PCR和Western blot显示,SMMC7721/HBx组在RNA及蛋白水平均有HBx的表达,而SMMC7721/pcDNA3组及SMMC7721组均无表达。与SMMC7721/pcD-NA3组及SMMC7721组相比,Western blot示SMMC7721/HBx组β-catenin、cyclinD1的表达水平较高,免疫细胞化学显示SMMC7721/HBx组β-catenin的表达水平较高,核染色较深,而SMMC7721/pcDNA3组及SMMC7721组之间则无明显差异。Westernblot和免疫细胞化学示一定浓度的舒林酸干预SMMC7721/HBx组和SMMC7721/pcDNA3组细胞48 h后可下调β-catenin和cy-clinD1的表达,而对SMMC7721/HBx组的下调较SMMC7721/pcDNA3组明显。结论HBx基因成功瞬时转染入SMMC7721细胞,激活Wnt信号通路,并同时上调cyclinD1的表达。舒林酸可通过下调β-catenin抑制肝癌细胞的Wnt信号通路,下调cyclinD1的表达,且HBx阳性的肝癌细胞对舒林酸较敏感。