PPARγ激动剂吡格列酮抑制胶质瘤细胞生长、凋亡的实验研究

目的探讨过氧化物酶体增长因子活化受体了激动剂（PPARγ）吡格列酮抑制胶质瘤细胞生长的机制。方法应用细胞增殖力测定、AO／EB荧光染色、流式细胞仪检测吡格列酮抑制胶质瘤细胞生长的情况。结果吡格列酮对胶质瘤细胞株U-251的生长有抑制作用,并呈时间与剂量依赖关系（P〈0．05）;可诱导胶质瘤细胞的凋亡,呈时间依赖关系（P〈0．05）,并出现细胞凋亡征象。结论PPARγ激动剂吡格列酮对胶质瘤细胞U-251具有生长抑制作用。其可诱导胶质瘤细胞凋亡可能是细胞生长抑制的机制之一。     

吡格列酮对HepG2细胞增殖和凋亡的影响及机制研究

目的观察吡格列酮对体外培养的HepG2细胞增殖和凋亡的影响,并探讨其是否通过PPARγ依赖途径发挥上述药理作用。方法将不同浓度的吡格列酮作用于体外培养HepG2细胞,以MTT比色法检测HepG2细胞增殖情况,以3H-TdR参入实验检测细胞DNA合成速率,采用RT-PCR和Western blot检测PPARγmRNA和蛋白的表达,以流式细胞术检测细胞凋亡和细胞周期;同时观察PPARγ特异性拮抗剂GW9662和(或)瞬时转染pSG5-PPARγ真核表达质粒对吡格列酮细胞增殖作用的影响;并将PPARγ小干扰RNA(pGCsi-PPARγ)表达质粒稳定转染HepG2细胞,观察PPARγ沉默后吡格列酮对HepG2细胞增殖作用的影响。结果吡格列酮作用于HepG2细胞后,导致HepG2细胞的增殖受到抑制、DNA合成速率减慢,并诱导细胞凋亡,呈一定的剂量依赖关系;在此过程中,G0/G1期细胞比例明显增加,S期细胞比例明显减少,但PPARγmRNA和蛋白的表达没有变化;GW9662部分拮抗吡格列酮的增殖抑制作用,但转染pSG5-PPARγ真核表达质粒可以逆转GW9662的作用;吡格列酮在高浓度(20μmol.L-1)时对pGCsi-PPARγ表达质粒稳定转染的HepG2细胞仍表现出增殖抑制作用。结论吡格列酮能够抑制HepG2细胞的增殖并诱导凋亡,具有潜在的抗瘤作用,这种作用与其诱导细胞G0/G1期的停滞有关,PPARγ依赖和非依赖途径参与上述过程。     

吡格列酮对过氧化氢诱导的乳鼠心肌细胞凋亡的抑制作用

目的观察吡格列酮对乳鼠心肌细胞凋亡的抑制作用及其可能作用机制。方法采用培养的新生大鼠乳鼠心肌细胞制备H2O2200μmol·L-1氧化损伤模型。实验分为正常对照组、模型组、吡格列酮组(0.1,1及10μmol·L-1)、吡格列酮(10μmol.L-1)+GW9662(10μmol·L-1)组、维拉帕米1μmol.L-1组。MTT法测心肌细胞的活力;采用硫代巴比妥酸比色法、黄嘌呤氧化酶法分别测定心肌细胞中脂质过氧化产物丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;流式细胞仪检测心肌细胞的凋亡率;采用Till阳离子测定系统,以Fura-2/AM为荧光探针,观察心肌细胞[Ca2+]i瞬间变化。结果H2O2200μmo.lL-1作用于心肌细胞12h能引起心肌细胞凋亡。吡格列酮浓度依赖性地增加受损心肌细胞的活力及SOD活性,降低MDA含量。吡格列酮10μmol·L-1抑制作用最明显,其与维拉帕米1μmol·L-1有相似的抑制作用,二者都可以减少心肌细胞的凋亡率,降低由H2O2诱导的升高的[Ca2+]i静息水平及频率。过氧化物酶体增殖物激活受体PPARγ受体特异性拮抗剂GW966210μmol.L-1能拮抗吡格列酮的部分抑制作用,但不影响吡格列酮对[Ca2+]i的瞬变作用。结论吡格列酮可以抑制H2O2诱导的乳鼠心肌细胞凋亡,其作用机制可能与其抗脂质氧化和减少细胞内钙超载有关,其抑制作用部分是通过PPARγ受体介导的。     

吡咯列酮对糖尿病大鼠心脏缺血再灌注的保护作用及机制

目的研究吡咯列酮对糖尿病大鼠心脏缺血再灌注的保护作用及机制。方法链脲佐菌素腹腔注射建立糖尿病大鼠模型,将糖尿病大鼠45只随机分为5组:假手术组,缺血再灌注组,吡格列酮5 mg/kg组,吡格列酮10 mg/kg组和吡格列酮20 mg/kg组,每组9只,利用体内结扎左前降支的方法建立缺血再灌注损伤模型,取大鼠心肌组织,检测细胞凋亡、丙二醛(MDA)、超氧化物歧化酶(SOD)、Bax、Bcl-2、Cytochrome c和Smac/DIABLO和半胱氨酸天冬酶9、3(Caspase 9、3)的变化。结果与缺血再灌注组相比,吡格列酮5、10和20 mg/kg可呈剂量依赖性减少MDA含量、Bax蛋白表达、Caspase 9、3酶活性,增加SOD酶活性和Bc-l2蛋白表达,抑制细胞凋亡。结论吡格列酮预处理可降低糖尿病大鼠心肌缺血再灌注后细胞的氧化损伤水平,下调线粒体凋亡蛋白表达,减少心肌细胞凋亡数以起到心肌保护作用。     

吡格列酮对高脂诱导胰岛素抵抗大鼠脂肪组织脂联素及其受体表达的影响

目的:探讨吡格列酮对高脂诱导胰岛素抵抗大鼠脂肪组织脂联素及其受体表达的影响。方法:使用高脂饲料喂养Wistar大鼠诱导胰岛素抵抗模型,观察吡格列酮预防绐药对大鼠脂肪组织抵抗素、脂联素及脂联素受体R1表达的影响。HepG2肝细胞加入不同浓度的软脂酸(100,200,400μmol·L-1)和吡格列酮培养后,观察脂联素受体R1和R2表达的改变。结果:在体实验模型组脂肪组织抵抗素和脂联素表达的灰度均显著低于正常组(P<0．01),脂联素受体表达与正常组无显著性差异。与模型组比较,吡格列酮组脂联素表达的灰度显著升高(P<0．05),抵抗素和R1表达的灰度比无明显变化(P>0．05)。离体实验软脂酸及吡格列酮对HepG2细胞R1的表达无明显改变;200和400μmol·L-1软脂酸可明显抑制HepG2细胞R2的表达,吡格列酮可以逆转该改变。结论:吡格列酮通过上调脂联素及脂联素受体R2的表达改善高脂诱导胰岛素敏感性的降低。     

吡格列酮对Aβ_(25-35)引起的皮层神经元损伤保护作用部分机制的研究

目的研究吡格列酮对抗淀粉样β蛋白片段25-35(Amyloid-β,Aβ25-35)所致培养皮层神经元损伤作用的机制。方法取培养7d大鼠乳鼠大脑皮层神经元,Aβ组加入Aβ25-35(20μmol.L-1)作用24h;吡格列酮组和各种阻断剂组,先加入吡格列酮(0.1、1、10μmol.L-1)或各种阻断剂作用1h,然后加入Aβ25-35(20μmol.L-1)作用24h;正常对照组加入等量培养基。MTT法测定细胞存活率;免疫荧光染色法测定活性的caspase-3细胞内定位;Westernblot检测活性的caspase-3表达水平;Griess法测定培养细胞上清液中一氧化氮(NO)含量。结果神经元经NSE和NF200免疫荧光鉴定,其阳性率可达90%以上。Aβ25-35(20μmol.L-1)可使神经元细胞存活率下降、caspase-3表达明显增加,同时神经元培养液中的NO含量也明显增加。吡格列酮可明显抑制Aβ25-35诱导的神经元细胞存活率下降、抑制caspase-3表达的增加,吡格列酮还可明显抑制Aβ25-35诱导的神经元培养液中NO含量增加,且呈浓度依赖性。GW9662(10μmol.L-1)能明显对抗吡格列酮对Aβ25-35诱导的神经元细胞存活率下降、活性的caspase-3表达增加、NO增加的抑制作用。SP600125(5μmol.L-1)、SB203580(20μmol.L-1)和SMT(1mmol.L-1)可明显对抗Aβ25-35诱导的神经元细胞存活率下降及培养液中NO含量增加。结论吡格列酮能够明显的抑制Aβ25-35引起的皮层神经元损伤作用,这种作用可能与激活PPARγ受体、抑制JNK信号传导通路和p38MAPK信号传导通路有关。     

吡格列酮对高胆固醇模型大鼠脂肪组织细胞中肿瘤坏死因子-α分泌及其mRNA表达的影响

目的:研究吡格列酮对高胆固醇模型大鼠脂肪组织细胞中肿瘤坏死因子-α(TNF-α)分泌及其mRNA表达的影响。方法:将30只高胆固醇饮食8周的大鼠随机分为高胆固醇组(n=15)和吡格列酮组(n=15),前者继续给予高胆固醇饮食,后者在此基础上加吡格列酮3mg.kg-1.d-1,连续4周;另设喂普通饲料12周的对照组(n=15)。处死大鼠并检测血脂、血清TNF-α水平及其mRNA表达等指标。另取正常脂肪细胞加入脂多糖和不同浓度的吡格列酮(0.1、1.0、10.0μmol.L-1)中,测定脂肪组织细胞中的TNF-α水平及其mRNA表达。结果:与高胆固醇组比较,吡格列酮组可明显降低血清TNF-α水平及减弱其mRNA表达,但对血糖和血脂水平几乎无影响。上述吡格列酮各浓度组可呈浓度依赖性抑制脂多糖诱导TNF-α分泌及其mRNA表达。结论:吡格列酮可降低高胆固醇模型大鼠血清和脂肪组织中TNF-α水平。     

高糖环境中吡格列酮对MC3T3-E1成骨细胞的作用及其机制

目的观察高糖环境下吡格列酮对MC3T3-E1成骨细胞的作用并探讨其可能机制。方法高糖(22.5 mmol·L~(-1))环境培养MC3T3-E1细胞,分为对照组,吡格列酮2.5、5、10μmol·L~(-1)组,干预24、48 h。检测细胞增殖活性、凋亡率、骨钙素和碱性磷酸酶(ALP)分泌水平,以及过氧化物酶体增殖物激活受体γ(PPARγ)、成骨因子runt相关基因2(Runx2)和骨形态蛋白2(BMP-2)mRNA的表达水平。并分析PPARγ、Runx2的表达与骨钙素、ALP、BMP-2的相关性。结果在相同干预时限,吡格列酮各组MC3T3-E1成骨细胞增殖活性、骨钙素和ALP的分泌水平、Runx2 mRNA和BMP-2 mRNA的表达均低于对照组,凋亡率和PPARγmRNA的表达高于对照组(P<0.05)。随吡格列酮浓度增加,细胞增殖活性、骨钙素和ALP的分泌、Runx2 mRNA和BMP-2 mRNA的表达均降低,而细胞凋亡率和PPARγmRNA的表达增高(P<0.05)。与干预24 h相比,干预48 h时相同浓度吡格列酮组细胞增殖活性,骨钙素和ALP的分泌水平,PPARγ、Runx2、BMP-2 mRNA的表达或无变化或略增加。结论高糖环境下吡格列酮对成骨细胞有损害作用,促进PPARγ表达、抑制Runx2的表达可能为其作用机制之一。     

吡格列酮对谷氨酸诱导皮质神经元损伤保护作用及其抑制JNK信号的机制

目的观察吡格列酮对谷氨酸所致培养皮质神经元损伤的保护作用及作用机制。方法大鼠乳鼠大脑皮质神经元,培养7d后用于实验。实验分为对照组、谷氨酸组、谷氨酸+吡格列酮组、谷氨酸+SP600125组、SP600125组。用MTT法测定细胞活力;Hoechst33258核染色观察细胞凋亡的形态学改变;免疫荧光染色法检测磷酸化活化转录因子2(phospho-ATF2)的表达;Western blot检测磷酸化JNK1和JNK1总量的蛋白表达水平。结果谷氨酸(100μmol.L-1)作用24h可使体外培养的皮质神经元细胞活力明显下降,细胞凋亡百分比明显增加,磷酸化JNK1蛋白水平(谷氨酸作用2h后检测)和磷酸化ATF2表达明显增加。吡格列酮明显对抗谷氨酸引起的皮质神经元损伤,同时明显抑制谷氨酸引起的磷酸化JNK1及磷酸化ATF2表达增多。JNK抑制剂SP600125明显对抗谷氨酸引起的神经元损伤及phos-pho-ATF2表达增多。结论吡格列酮对谷氨酸引起的培养皮质神经元损伤具有明显的保护作用,吡格列酮的保护作用与抑制JNK信号转导通路有关。     

吡格列酮对高糖高胰岛素诱导的心肌细胞肥大的影响

目的　利用体外培养的乳鼠心肌细胞 ,观察吡格列酮对高浓度葡萄糖与高浓度胰岛素共同诱导的肥大心肌细胞的影响 ,进一步推测吡格列酮对糖尿病并发心肌肥大的可能作用及作用机制。方法　以培养的乳鼠心肌细胞为模型分组给药后 ,用Lowrys法测心肌细胞的蛋白质含量 ;用 [3 H]leucine标记法测定心肌细胞蛋白的合成 ;利用计算机图像分析系统测心肌细胞的体积 ;用显微镜目镜计数心肌细胞搏动的频率。结果　 10 μmol·L-1浓度的吡格列酮在对高糖高胰岛素诱导的肥大心肌细胞的蛋白含量、蛋白合成及体积均有显著的抑制作用。其抑制肥大的效果比维拉帕米更为明显 ;同时观察到吡格列酮同维拉帕米一样有抑制心肌细胞搏动的作用。结论　吡格列酮能有效抑制高糖高胰岛素诱导的心肌细胞肥大。这种作用可能是通过作用于PPARγ来实现的。     

Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in multiple myeloma

The activation of proliferator-activated receptor gamma (PPAR-gamma) by its natural and synthetic ligands induces apoptosis in several tumor cell lines, including malignant B-lineage cells. We investigated whether treatment with pioglitazone (PGZ), rosiglitazone (RGZ) or 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) inhibited tumor cell growth in five human multiple myeloma cell lines (LP-1, U-266, RPMI-8226-S, OPM-2 and IM-9) and human bone marrow myeloma cells expressing PPAR-gamma protein. MTT assays revealed growth arrest induced by the natural activator of PPAR-gamma 15d-PGJ2 and a lower antiproliferative effect with thiazolidinediones (PGZ and RGZ) in a dose-dependent manner. Induction of apoptosis was indicated by Annexin-V staining. At a dose of 50 microM, 15d-PGJ2 led to a high rate of apoptosis in all cell lines (60-92%). Furthermore, induction of apoptosis in sorted bone marrow plasma cells from myeloma patients was detected. Thiazolidinediones comprise anti-myeloma activity in vitro and should be explored further for the treatment of multiple myeloma.     

Dietary isothiocyanate iberin inhibits growth and induces apoptosis in human glioblastoma cells

In this study, we evaluated the antiproliferative and proapoptotic effects of the isothiocyanate iberin, a bioactive agent in Brassicaceae species, in human glioblastoma cells. The human glioblastoma cell cultures were treated with different concentrations of iberin and tested for growth inhibition, cytotoxicity, induction of apoptosis, and activation of caspases. Iberin inhibited growth of tumor cells in cell proliferation assays, enhanced cytotoxicity, and induced apoptosis by activation of caspase-3 and caspase-9. Findings from this study could provide a basis for potential usefulness of the diet-derived isothiocyanate iberin as a promising therapeutic micronutrient in the prevention/intervention of brain tumors.     

A novel PPAR alpha／gamma dual agonist inhibits cell growth and induces apoptosis in human glioblastoma T98G cells

AIM: To examine the effect of a novel peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist TZD 18 on cell proliferation and apoptosis in human glioblastoma T98G cells and its possible mechanism. METHODS: RTPCR, MTT, TUNEL, Flow cytometry, and Western blot analysis were employed. RESULTS: TZD18 inhibited the growth of T98G cells in a concentration-dependent manner, which was associated with a GI to S cell cycle arrest. Besides, significant apoptosis was induced after treatment with a non-toxic dose of TZD 18. During the process, the expression of Bcl-2 protein was down-regulated, while that of Bax and p27^kip proteins was up-regulated, and the activity of caspase-3 was elevated. However, this effect appeared to be PPARα and PPARγ/independent since their antagonists could not reverse this effect. CONCLUSIONS: TZD18, a novel PPARα/γ dual agonist, inhibited cell growth and induce apoptosis in human glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD18 in the treatment of glioblastoma.     

Ardipusilloside I induces apoptosis in human glioblastoma cells through a caspase-8-independent FasL/Fas-signaling pathway

Ardipusilloside I, a triterpenoid saponin isolated from Ardisia pusilla A. DC, suppresses the growth of a variety of cancer cells, and has certain immunomodulative properties. Herein, we investigated its effect on glioblastoma cell line U87MG cells and primary cultured human glioblastoma cells, and examined the underlying mechanism of action. Ardipusilloside I substantially decreased the number of viable cells of both cell lines in a time- and concentration-dependent manner, with a similar IC(50) of 4.05μM. Microscopy revealed apoptotic characteristics, including chromatin condensation and cell nucleus fragmentation, demonstrating that ardipusilloside I-induced apoptosis. Ardipusilloside I exposure also gradually increased the sub-G1 fraction (the apoptotic cell population) and an S phase-arrest of both glioblastoma cells. Furthermore, ardipusilloside I increased the expression of Fas and its ligand (FasL), and enhanced the activation of caspase-8 and caspase-3. Additionally, we observed a significant decreased apoptosis after the trigger effection of FasL was abolished by the neutralization antibody anti-FasL antibody and an unchanged apoptosis level when the activation of caspase-8 was interrupted by specific inhibitor z-IETD-fmk, which suggested that a casepase-8 independent FasL/Fas-signaling-mediated death receptor pathway is involved. These data suggested that ardipusilloside I could be developed as a chemotherapeutic agent for the management of gliomas.     

Functionalized glycomers as growth inhibitors and inducers of apoptosis in human glioblastoma cells

The effects of functionalized aryl beta-D-glycopyranosides (glycomers) on the proliferation, survival, and apoptosis of human glioblastoma cells in culture were evaluated as a way to control tumor progression. The results showed that inhibition of growth and/or induction of apoptosis can be achieved by these molecules in human glioblastoma cells. Inhibition of DNA synthesis precedes induction of apoptosis and growth inhibition. The substituents at C-1, C-2, C-3,C-4, and C-6 on the pyranosidic scaffold are important to modulate the action and the efficacy of these molecules. Human fibroblasts and brain-derived endothelial cells were less sensitive to glycomers than tumor cells. Thus, functionalized aryl beta-D-glycopyranosides represent a new class of molecules potentially able to control the progression of brain tumors.     

Modulation of the cell cycle and induction of apoptosis in human cancer cells by synthetic bile acids

In this paper, we will outline the current understanding of cell cycle modulation and induction of apoptosis in cancer cells by natural and synthetic bile acid. Bile acid homeostasis is tightly regulated in health, and their cellular and tissue concentrations are restricted. However, when pathophysiological processes impair their biliary secretion, hepatocytes are exposed to elevated concentrations of bile acids which trigger cell death. In this context, we developed several newly synthesized bile acid derivatives. These synthetic bile acids modulated the cell cycle and induced apoptosis in several human cancer cells similar to natural bile acids. In human breast and prostate cancer cells with different tumor suppressor p53 status, synthetic bile acid-induced growth inhibition and apoptosis were associated with up-regulation of Bax and p21(WAF1/CIP1) via a p53-independent pathway. In Jurkat human T cell leukemia cells, the synthetic bile acids induced apoptosis through caspase activation. In addition to this, the synthetic bile acids induced apoptosis in a JNK dependent manner in SiHa human cervical cancer cells, via induction of Bax and activation of caspases in PC3 prostate cancer cells and induction of G1 phase arrest in the cell cycle in HT29 colon cancer cells. Moreover, they induced apoptosis in four human glioblastoma multiform cell lines (i.e., U-118MG, U-87MG, T98G, and U-373MG) and one human TE671 medulloblastoma cells. In addition to this, a chenodeoxycholic acid derivative, called HS-1200, significantly decreased the growth of TE671 medulloblastoma tumor size and increased life span in non-obese diabetic and severe combined immunodeficient (NOD/SCID) mice. Therefore, these new synthetic bile acids, which are novel apoptosis mediators, might be applicable to the treatment of various human cancer cells.     

吡格列酮对高糖高脂诱导大鼠H9C2心肌细胞凋亡的 影响及其机制探讨

目的 探讨吡格列酮对高糖高脂诱导H9C2心肌细胞凋亡的影响及其机制。方法 体外培养H9C2心肌 细胞,通过 CCK-8 法进行细胞毒性试验分别确定高糖（HG）和棕榈酸（PA）最佳干预浓度,选取 0.1 mmol/L PA 和 50 mmol/L HG共同培养细胞建立高糖高脂损伤模型,不同浓度吡格列酮（PGZ）干预高糖高脂损伤细胞12、24及48 h 后通过CCK-8试验选取有效的干预浓度和干预时间。随后细胞分为：对照组（25 mmol/L葡萄糖）、溶剂组（棕榈酸溶 剂+二甲基亚砜）、HGPA 组（50 mmol/L 葡萄糖+0.1 mmol/L PA）、H-PGZ 组（10 μmol/L PGZ+HGPA）和 L-PGZ 组 （5 μmol/L PGZ+HGPA）,采用AnnexinV-FITC/PI双染法检测细胞凋亡率;DCFH-DA法检测活性氧簇（ROS）水平;微 板法检测丙二醛（MDA）含量和超氧化物歧化酶（SOD）水平;Western blot法检测蛋白激酶B（T-AKT）、磷酸化蛋白激 酶B（P-AKT）、半胱氨酸天冬氨酸蛋白激酶3（Caspase3）、剪切化半胱氨酸天冬氨酸蛋白激酶3（C-Caspase3）、B-淋巴 细胞瘤基因-2（BCL-2）、BCL-2相关X蛋白（BAX）的蛋白表达。NAC（1 mmol/L N-乙酰半胱氨酸）+HGPA组和HGPA 组干预24 h后检测上述AKT通路及凋亡相关蛋白表达。结果 48 h内0、0.05、0.1、0.2、0.4 mmol/L PA组H9C2细胞活力 依次降低;12 h时,与25 mmol/L葡萄糖组比较,50、75以及100 mmol/L葡萄糖组细胞活力增加,24 h、48 h时25、35、50、 75、100 mmol/L葡萄糖组细胞活力依次增加;与对照组比较,48 h内HGPA组细胞活力降低（P＜0.05）;与HGPA组比 较,12 h时80 μmol/L组细胞活力降低（P＜0.05）,24 h时10 μmol/L PGZ组细胞活力增加,40、80 μmol/L PGZ组细胞活 力降低（P＜0.05）,48 h时5、10和20 μmol/L PGZ组细胞活力增加,40、80 μmol/L PGZ组细胞活力降低（P＜0.05）;与 对照组比较,HGPA组凋亡率、ROS、MDA、C-Caspase3、BAX表达明显升高,SOD、P-AKT、BCL-2表达降低（P＜0.05）; HGPA组、L-PGZ组、H-PGZ组的凋亡率、ROS、MDA、C-Caspase3、BAX依次降低,SOD、P-AKT、BCL-2表达依次升高 （P＜0.05）。与 HGPA 组比较,NAC+HGPA 组 C-Caspase3 表达降低,P-AKT、Caspase3 表达升高（P＜0.05）。结论 PGZ对ROS有抑制作用,可以促进AKT通路的活化,减轻高糖棕榈酸诱导的H9C2心肌细胞凋亡。     

NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-κB). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-κB activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT as well as in tumor photodetection (PDD). Our results show that inhibition of NF-κB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-κB inhibition. We found that apoptosis was induced by PDT but in an incomplete manner and that, unexpectedly, NF-κB inhibition reduced its level. Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-κB is found to have anti-necrotic functions in this context. The autophagic flux was also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of autophagy acts as a pro-survival mechanism confering protection against PDT-mediated necrosis. These data point out that 5-ALA-PDT has an interesting potential as a mean to treat glioblastoma and that inhibition of NF-κB renders glioblastoma cells more sensitive to the treatment.