青蒿素基于PI3K/AKT信号通路对人急性髓系白血病细胞凋亡的作用机制

目的分析青蒿素基于磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路对人急性髓系白血病(AML)细胞凋亡的作用机制。方法以44例AML患儿原代细胞及K562细胞株4株为研究样本,平均分为对照组、实验组(分别加入12.5、25.0、50.0μg/ml青蒿琥酯),细胞计数法观察72 h内细胞生长趋势,采用流式细胞术检测不同浓度青蒿琥酯对细胞凋亡的影响,免疫印迹法检测细胞凋亡相关蛋白(PI3K、AKT、P-AKT、Bcl-2、Bax、caspase-3、PTEN)的表达。结果 AML原代细胞、细胞株K562 24 h内细胞存活率≥80%,对照组AML原代细胞、细胞株K562 48～72 h细胞存活率仍≥70%,而实验组AML原代细胞、细胞株K562培养48 h细胞存活率均降至50%以下,且明显低于对照组(P<0.05);青蒿琥酯呈浓度依赖性诱导人AML原代细胞及K562细胞株凋亡,且25.0μg/ml组、50.0μg/ml组的细胞存活率低于12.5μg/ml组及对照组(P<0.05),25.0μg/ml组、50.0μg/ml组的细胞存活率比较差异无统计学意义(P>0.05)。培养48 h后,实验组原代细胞及K562细胞株的PI3K、P-AKT、Bcl-2均明显下调(P<0.05),而Bax、caspase-3、PTEN表达上调(P<0.05),且青蒿琥酯浓度为25.0μg/ml组各项指标变化最明显,AKT无明显变化(P>0.05)。结论青蒿素类衍生物青蒿琥酯可经PI3K/AKT信号通路调节其Bcl-2、Bax、caspase-3、PTEN等凋亡相关蛋白表达,促进人AML细胞凋亡,25μg/ml浓度时效果较佳。     

益景汤经PI3K/AKT/eNOS信号通路拮抗高糖诱导的视网膜血管内皮细胞损伤

目的 探讨益景汤对高糖诱导大鼠视网膜微血管内皮细胞损伤的拮抗作用及机制。方法 将大鼠视网膜微血管内皮细胞随机分为5组：对照组(CG)、高糖组(HG)、低浓度益景汤组(LYG)、中浓度益景汤组(MYG)、高浓度益景汤组(HYG)。细胞生长至80%～90%时，往高糖组及益景汤组培养基中加入33 mmol/L葡萄糖培养3 d造高糖内皮细胞损伤模型，第4天按分组加入相应正常糖培养基及各浓度益景汤培养24 h。使用CCK-8试剂盒检测内皮细胞活性，Transwell法观察内皮细胞迁移，荧光聚合酶链式反应(PCR)检测细胞间紧密连接蛋白ZO-1及内皮细胞磷脂酰肌醇三羟基激酶(PI3K)、苏氨酸蛋白激酶(AKT)、内皮型一氧化氮合酶(eNOS)的信使RNA(mRNA)表达。结果 高糖条件下，大鼠视网膜微血管内皮细胞活性降低，与对照组比较，差异有统计学意义(均P<0.05);与高糖组比较，低、中、高浓度益景汤组细胞活性均高于高糖组，差异均有统计学意义(均P<0.05)。高糖条件下，大鼠视网膜微血管内皮细胞迁移增强，与对照组比较，差异有统计学意义(P<0.05);与高糖组比较，低、中、...     

红景天苷通过AKT/mTOR信号通路对结肠癌细胞SW480增殖、凋亡和裸鼠移植瘤生长的影响

目的 探究红景天苷(salidroside, SAL)对结肠癌细胞SW480增殖、凋亡和裸鼠移植瘤生长的影响。方法 采用0、25、50、100μmol·L^-1剂量红景天苷处理SW480细胞,将细胞随机分为4组：SAL 0μmol·L^-1组、SAL 25μmol·L^-1组、SAL 50μmol·L^-1组和SAL 100μmol·L^-1组。克隆形成实验检测细胞克隆形成率;流式细胞仪检测细胞凋亡;Western blot检测Ki67、PCNA、Caspase-3、Caspase-9、PI3K、p-PI3K、AKT、p-AKT、mTOR、p-mTOR蛋白表达水平。建立结肠癌裸鼠移植瘤模型,裸鼠随机分为2组：Control组和Salidroside 50 mg·kg^-1组,检测裸鼠肿瘤重量,TUNEL染色检测裸鼠肿瘤细胞凋亡率,免疫组化染色检测Ki67、Caspase-3阳性细胞数。结果 体外实验中,与SAL 0μmol·L^-1组相比较,SAL...     

氟尿嘧啶通过激活促凋亡信号通路介导人肝癌细胞凋亡的治疗作用

目的研究氟尿嘧啶(5-Fu)通过激活促凋亡信号通路介导人肝癌细胞(HepG-2)凋亡的治疗作用。方法体外培养HepG-2细胞,分别在0(空白对照组)、40、80、160μM浓度5-Fu干预72 h,采用四甲基偶氮唑盐(MTT)法测定5-Fu对HepG-2的抑制作用,DAPI染色检查细胞形态学的改变,Western blot法测定内源性Fas蛋白以及cleaved-caspase-8表达水平。结果与空白对照组比较,5-Fu干预组明显抑制HepG-2的细胞增殖(P<0.01),诱导细胞凋亡。此外,5-Fu可有效上调HepG-2内源性Fas蛋白和cleaved-caspase-8表达水平(P<0.01)。结论氟尿嘧啶介导的抗肝癌作用是通过抑制HepG-2细胞增殖和激活内源性Fas信号通路而诱导癌细胞凋亡。     

黄酮类新化合物LFG-500通过调控MAPK和AKT/mTOR信号通路抑制人乳腺癌MCF-7细胞增殖

目的 考察黄酮类新化合物LFG-500对人乳腺癌MCF-7细胞的生长抑制作用,并初步探讨其抑制细胞增殖的作用机制。方法 体外培养MCF-7细胞,实验设置空白对照组,以及浓度为10、20、30μM的LFG-500处理组,处理细胞24 h。通过平板克隆形成实验检测LFG-500对细胞的增殖能力的抑制作用;利用Western blot实验检测LFG-500对MCF-7细胞内MAPK信号通路关键蛋白ERK/p-ERK、JNK/p-JNK、p38/p-p38及AKT/mTOR信号通路核心蛋白AKT/p-AKT、mTOR/p-mTOR的调节作用。结果 平板克隆形成实验结果显示,与对照组相比,LFG-500中、高剂量组MCF-7细胞增殖明显受到抑制（P <0.01）;Western blot结果显示,LFG-500可上调MCF-7细胞中MAPK信号通路核心蛋白p-JNK和p-p38的表达,下调p-ERK的表达（P <0.05）。此外,LFG-500也可抑制AKT/mTOR信号通路的核心蛋白p-AKT和p-mTOR的表达水平（P <0.05）。结论 LFG-500可能通过调控MAPK...     

洛铂在膀胱癌细胞中的抗肿瘤作用及通过PI3K/AKT信号通路促进凋亡的机制研究

目的研究洛铂在人类膀胱癌细胞中的抗肿瘤作用及促进其凋亡的相关分子机制。方法体外实验:Cell Counting Kit-8(CCK8)法检测洛铂对T24细胞增殖的影响;划痕实验检测洛铂对迁移的影响;Annexin V-FITC/PI双染色,通过流式细胞仪检测细胞的凋亡程度;蛋白免疫印迹法(WB)检测洛铂对凋亡相关蛋白表达的影响。体内实验:选取BALB/c裸鼠建立膀胱癌细胞皮下异种转移瘤模型,观察洛铂对肿瘤生长的影响;免疫组织化学检测观察相关凋亡蛋白的表达。结果体外实验:洛铂能够抑制膀胱癌细胞T24的增殖,抑制其迁移,同时促进其凋亡,凋亡相关蛋白Bax表达增加,Bcl-2表达减少,Cleaved-Caspase-3/Caspase-3升高,PI3K/AKT信号通路中PI3K表达减少,P-Akt/Akt降低。体内实验:洛铂给药组裸鼠转移瘤体积小于对照组且差异有统计学意义,免疫组织化学结果显示洛铂给药组凋亡相关蛋白Bax表达增加,Bcl-2表达减少,Cleaved-Caspase-3表达增加。结论洛铂在膀胱癌细胞中具有抗肿瘤作用,可能是通过PI3K/AKT信号通路发挥促凋亡作用。     

地塞米松通过ROS-PI3K/AKT/GSK3β信号通路诱导成骨细胞凋亡

目的:探讨地塞米松（Dex）对成骨细胞增殖和凋亡的影响及潜在的作用机制。方法:将人成骨细胞hFOB 1.19分为4组：对照组（不加药物）,Dex组（300 μM Dex处理48 h）,Dex+AA组（300 μM Dex+2 000 μM AA处理48 h）和Dex+NAC组（300 μM Dex+500 μM NAC...     

茶多酚对内毒素抑制人牙周膜成纤维细胞增殖的影响

目的 观察茶多酚对脂多糖(LPS)诱导下人牙周膜成纤维细胞(HPDLFs)增殖的影响.方法 采用组织块培养法培养原代HPDLFs并传代、免疫组化检测,取第5代细胞用于实验.将LPS及茶多酚分组,采用四甲基偶氮唑盐(MTT)法分别于24、48、72 h检测HPDLFs增殖活力.结果 免疫组化染色结果显示,所培养细胞的波形丝蛋白染色呈阳性表现,阳性部位位于胞质,角蛋白染色呈阴性表现.各浓度LPS组在24、48、72 h的光密度(OD)值(4 mg/L LPS组:0.323±0.007、0.345±0.010、0.437±0.007;20 mg/L LPS组:0.270±0.004、0.283±0.009、0.367±0.007; 100 mg/L LPS组:0.175±0.006、0.187±0.006、0.248±0.005;500 mg/L LPS组:0.088±0.004、0.091±0.006、0.153±0.009)与同时段空白对照组(0.306±0.008、0.333±0.007、0.399±0.007)组间比较差异均有统计学意义(均P＜0.05).100 mg/L LPS组和各浓度茶多酚组在24、48、72 h的OD值(100 mg/L LPS组:0.216±0.010、0.260±0.010、0.352±0.012; 100 mg/L LPS组+0.125 g/L茶多酚组:0.300±0.010、0.408±0.013、0.490±0.014;100 mg/L LPS组+0.25 g/L茶多酚组:0.333±0.012、0.416±0.010、0.532±0.012;100 mg/L LPS组+0.5 g/L茶多酚组:0.390±0.012、0.485±0.011、0.642±0.013;100 mg/L LPS组+1 g/L茶多酚组:0.368±0.010、0.481±0.006、0.621±0.007)与同时段空白对照组(0.450±0.012、0.528±0.011、0.687±0.010)组间比较,差异均有统计学意义(均P＜0.05);各浓度茶多酚组在24、48、72 h的OD值均低于同时段100 mg/L LPS组(均P＜0.05).结论 LPS抑制HPDLFs的增殖,茶多酚明显促进LPS诱导下HPDLFs的增殖,这提示茶多酚可应用于牙周炎的预防及治疗.     

莪术醇通过调控PI3K/AKT通路促进人肝癌HepG2细胞凋亡

目的探讨莪术醇促进人肝癌HepG2细胞凋亡的作用是否与PI3K/AKT通路有关。方法采用MTT法检测不同浓度(0、10、25、50、100μmol·L~(-1))莪术醇干预HepG2细胞24、48 h的增殖抑制率,Hoechst 33258染色法观察细胞核凋亡形态,Western blot法检测不同浓度莪术醇及PI3K/AKT通路阻断剂LY294002对HepG2细胞p-PI3K、p-AKT、Caspase-3蛋白表达的影响。结果莪术醇对HepG2细胞的增殖有明显抑制作用,呈浓度依赖性,但干预48 h对比24 h差异无统计学意义;Hoechst 33258染色发现,莪术醇干预后,同一视野下细胞数目明显减少,细胞透亮,部分细胞核碎裂,核固缩,呈现典型的凋亡形态学特征;Western blot结果显示,莪术醇能显著降低细胞p-PI3K、p-AKT蛋白的表达,上调凋亡执行蛋白Caspase-3的表达,与LY294002联用后表现出良好的协同作用,对各蛋白表达的调控较单独用药更加明显。结论莪术醇能通过抑制PI3K/AKT通路诱导人肝癌HepG2细胞凋亡。     

扁蓄苷对人乳腺癌MDA-MB-231细胞凋亡、周期及PI3K/AKT信号通路的影响

目的探讨扁蓄苷对乳腺癌MDA-MB-231细胞的凋亡、周期及PI3K/AKT信号通路的影响。方法以不同浓度的萹蓄苷作用于体外生长至对数期的MDA-MB-231细胞48 h后,采用噻唑蓝染色(MTT)法检测扁蓄苷对细胞增殖的影响,Hoechst 33258染色观察细胞染色质固缩情况,流式细胞术检测细胞周期,Western-blot检测PI3K/AKT信号通路核心蛋白PI3K、p-PI3K、AKT、p-AKT表达水平,RT-PCR技术检测通路下游细胞凋亡蛋白Bcl-2、Bcl-xl及周期相关蛋白CDK2基因表达情况。结果不同浓度的扁蓄苷(6.25、12.5、25、50、100μmol·L~(-1))作用于MDA-MB-231细胞48 h后,细胞增殖活性受到抑制(P <0.01),且具有浓度依赖性;扁蓄苷(12.5、50、100μmol·L~(-1))作用细胞48 h后,细胞核染色质固缩;当扁蓄苷浓度为50μmol·L~(-1)时,S期细胞所占百分比显著增高(P <0.05),当扁蓄苷浓度为100μmol·L~(-1)时,G2/M期细胞所占百分比显著增高(P <0.05);随着扁蓄苷浓度的增加,通路核心位点PI3K、p-PI3K、AKT、p-AKT蛋白表达水平明显降低(P <0.01),细胞凋亡相关蛋白Bcl-2和Bcl-xl、细胞周期蛋白CDK2基因表达水平下调(P <0.05)。结论扁蓄苷可抑制乳腺癌MDA-MB-231细胞增殖,使细胞周期阻滞于S期、G2/M期,并诱导细胞凋亡。其机制可能是通过抑制PI3K/AKT信号通路下调Bcl-2、Bcl-xl、及CDK2基因表达进而诱导人乳腺癌MDA-MB-231细胞凋亡。     

Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway

Emodin, a natural anthraquinone compound isolated from the rhizome of rhubarb, is reported to suppress the growth of tumor in many clinical situations. In this study, we focused on the effect of emodin in human breast cancer BCap-37 cells and further understand the underlying molecular mechanism in treating breast cancer. Using MTT assay and flow cytometry, we demonstrated the critical role of emodin in the suppression of the proliferation of BCap-37 cells based on a concentration-and time-dependent manner. The increase of apoptotic rate was also observed after incubation of BCap-37 cells on emodin at 20 microM and 50 microM for 48 h. The cells exhibited typical apoptotic features including cellular morphological change, chromatin condensation and membrane blebbing. The results of the study further showed that Bcl-2 level decreased, while Bax and cytosolic cytochrome c levels in sample cells increased after the emodin treatment by using Western blot. The decline in the Bcl-2/Bax ratio and the increase of cytosolic cytochrome c concentration were consistent with the increase of the apoptotic ratio. The results strongly suggest that the disruption of the mitochondrial signaling pathway was involved in emodin-induced apoptosis in BCap-37 cells.     

Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1

Background and objectivesAlthough apigenin exhibits various biological effects, its anti-inflammatory role in the periodontal field remains unknown. We examined the anti-inflammatory effects of apigenin and the underlying mechanism in nicotine- and lipopolysaccharide (LPS)-stimulated human periodontal ligament (hPDL) cells.Materials and methodsWestern blotting was used to examine the effect of apigenin (10–40 µM) on the LPS- and nicotine-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and heme oxygenase-1 (HO-1), as well as the phosphorylation of mitogen-activated protein kinases (MAPKs), in hPDL cells. Pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, and IL-12 were monitored using Griess reagents and ELISA.ResultsIncubation of hPDL cells with apigenin decreased LPS- and nicotine-induced HO-1 protein expression and activity. Apigenin significantly inhibited the nicotine- and LPS-induced production of NO, PGE₂, IL-1β, TNF-α, IL-6, and IL-12, and the upregulation of iNOS and COX-2 in hPDL cells. Hemin, a selective HO-1 inducer, reversed the apigenin-mediated suppression of nicotine- and LPS-induced NO, PGE₂ and cytokine production. Treatment with inhibitors of the phosphoinositide 3-kinase, MAPKs, p38, and JNK, as well as a protein kinase C inhibitor, blocked the anti-inflammatory effects of apigenin in nicotine- and LPS-treated cells.ConclusionsApigenin possesses anti-inflammatory activity in hPDL cells and works through a novel mechanism involving the action of HO-1. Thus, apigenin may have potential benefits as a host modulatory agent in the prevention and treatment of periodontal disease associated with smoking and dental plaque.     

4-NQO induces apoptosis via p53-dependent mitochondrial signaling pathway

4-Nitroquinoline N-oxide (4-NQO) as an UV-mimetic agent leading to DNA damage is a potent mutagen and carcinogen, and can induce apoptosis in various types of cells. However, the mechanism of apoptosis induced by 4-NQO is still not quite clarified. In this study we found that 4-NQO could not only induce apoptosis in KB cells, but also caused considerable damage to the mitochondrial membrane. Therefore, we inferred that 4-NQO might induce apoptosis through the mitochondrial signaling pathway resulting from DNA damage. Further investigation showed that the apoptosis induced by 4-NQO was p53-dependent. Furthermore, the expression levels of bax and bcl-2, closely related to mitochondrial signaling pathway, were up- and down-regulated, respectively. Meanwhile, the activity of caspase-9 and -3, lying in downstream of mitochondrial, was also enhanced. At the same time, the expression level of p21 also was increased by 4-NQO exposure, leading to the cell cycle arrested in G₁ phase. The results indicated that 4-NQO arrested cell cycle in G₁ phase, thus allowing enough time for DNA repair; on the other hand, if the cellular DNA were not repaired, apoptosis may follow through the p53-dependent mitochondrial signaling pathway, and mechanism of apoptosis induced by 4-NQO is not exactly the same that induced by UV radiation, as the later induces apoptosis through death receptors and mitochondrial signaling pathway.     

miR-552通过PTEN/AKT信号通路促进非小细胞肺癌A549细胞的恶性生物学行为

目的 探讨miR-552通过调控PTEN/AKT信号通路促进人非小细胞肺癌A549细胞的恶性生物学行为及其相关机制。方法 通过qRT-PCR检测人肺癌组织样本和人非小细胞肺癌A549细胞系中miR-552、PTEN mRNA的表达情况;通过Western blotting检测PTEN、AKT、p-AKT蛋白的表达情况;通过CCK-8检测miR-552表达对A549细胞增殖能力的影响;通过Transwell小室检测miR-552表达对A549细胞迁移和侵袭能力的影响;通过流式细胞术检测miR-552表达对A549细胞凋亡能力的影响。结果 miR-552在肺癌组织和A549细胞中的表达显著上调。过表达miR-552可显著促进A549细胞的增殖、迁移和侵袭,并抑制细胞凋亡,而抑制其表达则结果相反。与癌旁组织相比,肺癌组织中PTEN表达显著下调。过表达miR-552可下调PTEN蛋白表达,上调p-AKT蛋白表达,对AKT蛋白无影响,而抑制其表达则结果相反。结论 miR-552可能通过PTEN/AKT信号通路促进人非小细胞肺癌A549细胞的恶性生物学行为。     

JNK信号通路通过介导细胞凋亡对肺纤维化的调控作用

目的观察肺纤维化中肺组织caspase-3和磷酸化c-Jun氨基末端激酶(p-JNK)蛋白表达的变化,并探讨JNK信号转导通路对肺纤维化的调控作用。方法 72只健康雄性Wistar大鼠随机分为正常对照组(N组)、肺纤维化模型组(M组),肺纤维化+JNK抑制剂干预组(I组),每组24只,分别于第3、7、14、28天处死,每组6只。留取肺组织,对其行苏木素-伊红(HE)染色,观察其病理学改变,碱水解法测定其中羟脯氨酸的含量,免疫组织化学法测肺组织中caspase-3和p-JNK的变化。结果模型组早期肺泡炎症明显,后期肺组织实变,caspase-3和p-JNK蛋白表达含量均显著增加(P<0.05),14d时达峰值。干预组能明显阻断JNK的激活(P<0.05),干预组caspase-3表达较模型组显著减少(P<0.05),14d时减少最明显。结论细胞凋亡是肺纤维化的一个重要病理组织学特点。JNK信号转导通路在肺纤维化中被激活,发挥促细胞凋亡效应。     

人牙周膜细胞接种于纳米-羟基磷灰石上的形态学研究

目的观察人牙周膜细胞接种于三维多孔纳米-羟基磷灰石上的组织形态学表现。方法将原代培养的人牙周膜细胞接种于三维多孔纳米-羟基磷灰石上，培养15天后，采用扫描电子显微镜观察细胞的生长情况，探讨两者的复合情况。结果作为种子细胞的人牙周膜细胞接种到支架材料上后，细胞粘附充分，生长旺盛，并有钙结节和少量胶原纤维形成。结论三维多孔纳米羟基磷灰石支架材料是一种比较符合牙周组织工程学条件的支架材料。     

Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway

Ghrelin is a 28-amino-acid peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR) and strongly stimulates the release of growth hormone from the hypothalamus–pituitary axis. Previous studies have identified the important physiological effects of ghrelin on bone metabolism, such as regulating proliferation and differentiation of osteoblasts, independent of GH/IGF-1 axis. However, research on effects and mechanisms of ghrelin on osteoblast apoptosis is still rare. In this study, we identified expression of GHSR in MC3T3-E1 cells and determined the effects of ghrelin on the apoptosis of osteoblastic MC3T3-E1 cells and the mechanism involved. Our data demonstrated that ghrelin inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as determined by terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate nick end-labeling (TUNEL) and ELISA assays. Moreover, ghrelin upregulated Bcl-2 expression and downregulated Bax expression in a dose-dependent manner. Our study also showed decreased activated caspase-3 activity under the treatment of ghrelin. Further study suggested that ghrelin stimulated the phosphorylation of ERK and AKT. Pretreatment of cells with the ERK inhibitor PD98059, PI3K inhibitor LY294002, and GHSR-siRNA blocked the ghrelin-induced activation of ERK and AKT, respectively; however, ghrelin did not stimulate the phosphorylation of p38 or JNK. PD90859, LY294002 and GHSR-siRNA attenuated the anti-apoptosis effect of ghrelin in MC3T3-E1 cells. In conclusion, ghrelin inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, which may be mediated by activating the GHSR/ERK and GHSR/PI3K/AKT signaling pathways.     

Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial pathway in human hepatic cells: A proteomic study

Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated compounds, and exposure to it has been associated with a number of adverse health effects. However, the molecular mechanisms involved in PFOA toxicity are still not well characterized. In the present study, flow cytometry analysis revealed that PFOA induced oxidative stress, cell cycle arrest and apoptosis in human non-tumor hepatic cells (L-02). Furthermore, we investigated the alterations in protein profile within L-02 cells exposed to PFOA, aiming to explore the mechanisms underlying PFOA hepatotoxicity on the proteome level. Of the 28 proteins showing significant differential expression in response to PFOA, 24 were down-regulated and 4 were up-regulated. This proteomic study proposed that the inhibition of some proteins, including GRP78, HSP27, CTSD and hnRNPC may be involved in the activation of p53, which consequently triggered the apoptotic process in L-02 cells. Induction of apoptosis via the p53-dependent mitochondrial pathway is further suggested as one of the key toxicological events occurring in L-02 cells under PFOA stress. We hope these data will shed new light on the molecular mechanisms responsible for PFOA-mediated toxicity in human liver cells, and from such studies useful biomarkers indicative of PFOA exposure could be developed.