Evidences of the involvement of Bak, a member of the Bcl-2 family of proteins, in active coeliac disease

Apoptosis of enterocytes is a feature that characterises the development of lesions in coeliac disease (CD). However, the intracellular pathways that lead to apoptosis of enterocytes have not been completely clarified. Bak is a member of the Bcl-2 family of proteins that acts as an endogenous promoter of apoptosis in normal enterocytes. However, its role in coeliac lesions has not been explored. We used small intestinal mucosa from patients with CD to evaluate the differential expression of members of the Bcl-2 family of proteins. Gene expression of Bak was analysed by RT-PCR of biopsies from 14 patients with untreated CD and from 19 controls without CD. In these samples, we also investigated the localisation of the Bak protein by immunohistochemistry and its apoptotic activity. In patients with untreated CD there was a 2.3-fold higher expression of Bak mRNA (p = 0.026), without significant differences in the expression of related genes bax or bcl-2. The higher expression of interferon gamma (IFN-gamma) (p = 0.036) and the higher number of apoptotic cells identified by the TUNEL method (p = 0.032) confirmed the proapoptotic status in the intestinal mucosa of CD patients. We found a significant positive correlation (p < 0.0001) between the expression of IFN-gamma and Bak mRNA in patients with untreated CD. The expression of Bak protein was higher in patients with CD, and the immunoreactivity was almost restricted to the epithelium. We found that Bak mRNA and its protein were overexpressed in the intestinal lesions of CD patients and that IFNgamma confers increased susceptibility for enterocytes to undergo apoptosis via upregulation of Bak.     

Enforced expression of the apoptosis inhibitor Bcl-2 ablates tolerance induction in DNA-reactive B cells through a novel mechanism

How self tolerance is maintained during B cell development in the bone marrow has been a focal area of study in immunology. Receptor editing, anergy and clonal deletion all play important roles in the regulation of autoimmunity in the immature population. The mechanisms of tolerance induction in the periphery, however, are less well characterized. Overexpression of the apoptosis inhibitor Bcl-2 rescues autoreactive B cells from deletion and can contribute to the development of autoimmune disease in certain genetic backgrounds. Using a peptide-induced autoimmunity model, we recently identified a peripheral tolerance checkpoint in antigen-activated B cells that have undergone class switching and somatic hypermutation. At this checkpoint, receptor editing, induced by antigen engagement, dampened the autoantibody response. In this study, we show that receptor editing fails to be induced in antigen-activated DNA-reactive B cells that overexpress Bcl-2 (Bcl-2 Tg). The failure to induce RAG and receptor editing is likely due, at least partially, to the lack of self antigen. First, the levels of circulating DNA and of apoptotic bodies in the spleen of Bcl-2 Tg mice are significantly lower than in control mice. Second, in Bcl-2 Tg mice, RAG can be induced in a population of antigen-activated B cells by providing exogenous soluble antigen. These data suggest that, in addition to its anti-apoptotic activity, Bcl-2 may indirectly inhibit tolerance induction in B cells acquiring anti-nuclear antigen reactivity after peripheral activation by limiting the availability of self antigen.     

Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.     

A Portrait of the Bcl-2 Protein Family: Life,Death, and the Whole Picture

The Bcl-2 family of proteins are important regulators of cell death. They are comprised of two opposing factions, the proapoptotic versus the antiapoptotic members. Both are required for normal development and cellular homeostasis of the immune system and other tissues. However, in certain circumstances they may participate in the development of disease.     

Apoptosis and occurrence of Bcl-2, Bak, Bax, Fas and FasL in the developing and adult rat endocrine pancreas

Apoptotic cell death is thought to play a crucial role in the manifestation of insulin- and non-insulin dependent diabetes mellitus. Therefore, apoptosis and apoptotic markers were studied in the rat endocrine pancreas to get insight into the possible life cycle of Langerhans islets.The islets were investigated at 13 time points between day E19 and 18 months. At each time point, histologic sections were treated with the direct fluorescein-labelled TUNEL method and immunostained for pancreatic hormones (glucagon, insulin), apoptotic promoters (Bak, Bax, Fas, Fas Ligand) as well as for the anti-apoptotic peptide Bcl-2. All tissue sections were investigated using confocal laser scanning microscopy under identical settings for semiquantitative estimation of staining intensity. TUNEL-positive cells occurred in all pre- or postnatal stages.The findings indicated a biphasic apoptotic activity in the endocrine pancreas during the lifetime of rats. The first phase began at E19 and peaked at P5 accompanied by a considerable increase in Bak fluorescence staining intensity, while the second phase began at P30 and peaked at 18 months with increasing amounts of Fas and FasL staining intensities in the islet cells. The presented in situ data may be important for understanding the increased age-related vulnerability of islet cells and for studies of isolated and cultivated rat islets. Accepted: 9 May 2000     

Amyloid precursor protein, heat-shock proteins, and Bcl-2 form a complex in mitochondria and modulate mitochondria function and apoptosis in N2a cells

Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis.     

The expression of Bcl-2 in adenomyosis and its effect on proliferation,migration, and apoptosis of endometrial stromal cells

Adenomyosis is a common gynecologic disease that severe impact on women. Previous studies have found that Bcl-2 abnormally expressed in adenomyosis. However, the exact mechanisms of Bcl-2 in the pathogenesis of adenomyosis are unclear. In this study, we are to explore the effect of Bcl-2 on proliferation, migration, and apoptosis of endometrial stromal cells. The expression of Bcl-2 were evaluated by Western blot and RT-qPCR. We used RNA interference to silence Bcl-2 gene of endometrial stromal cells, and then Cell Counting Kit(CCK-8), cell scratch repair test, and Annexin V-APC/propidium iodide (PI) staining were performed to detect the cell viability, migration ability and apoptotic rate. The results of the present study revealed that the expression of Bcl-2 was evidently higher than that in control group. After silencing the Bcl-2 gene, the cytoactive and migration ability of endometrial stromal cells of adenomyosis decreased, and the apoptotic rate increased. In conclusion, Bcl-2 is overexpressed in adenomyosis and participate in the pathogenesis of adenomyosis. Bcl-2 may be a potential novel target for adenomyosis treatment.     

急性心肌梗死晚期再灌注后心肌细胞凋亡与Bcl-2、Bax 蛋白表达的研究

目的:探讨犬急性心肌梗死后晚期再灌注对梗死周边缺血区心肌细胞凋亡及凋亡相关蛋白Bcl-2、Bax表达的影响。方法:健康成年杂交犬28只,全麻下常规开胸暴露冠状动脉后随机分为3组:假手术组(n=8),急性心肌梗死组(n=10)、晚期再灌注组(n=10)。假手术组仅行左冠状动脉前降支下穿过丝线而不结扎冠状动脉,急性心肌梗死组行左冠状动脉前降支高位永久结扎,晚期再灌注组在高位结扎左冠状动脉前降支6 h后松解结扎线予以再灌注6 h。共有23只犬模型制作成功。各组犬均于术后12 h处死,采集心肌标本。使用TUNEL法检测心肌细胞凋亡,免疫组化染色和Western blotting蛋白印迹分析Bcl-2、Bax在心肌细胞中表达情况。结果:晚期再灌注组心肌细胞凋亡数较急性心肌梗死组明显减少(P<0.05),但两组心肌细胞凋亡数均高于假手术组(P<0.01)。与假手术组相比,急性心肌梗死组和晚期再灌注组Bcl-2蛋白的表达均升高(P<0.01),其中在晚期再灌注组的表达略多于急性心肌梗死组,但无显著差异(P>0.05)。Bax蛋白在晚期再灌注组的表达高于假手术组(P<0.01),但低于急性心肌梗死组(P<0.05)。结论:急性心肌梗死后晚期再灌注可以减少梗死周边缺血区心肌细胞凋亡,其机制可能与心肌细胞表达Bax蛋白减少有关。     

赤芍总甙对Bcl-2、c-myc基因表达影响及诱导细胞凋亡机制研究

目的：探讨赤芍总甙（TGC）诱导肿瘤细胞凋亡机制，为TGC的开发应用提供实验依据。方法：采用流式细胞仪测定细胞凋亡，SABC免疫组化法检测Bcl-2蛋白表达，原位杂交法测定c—myc mRNA表达，电镜观察凋亡小体。结果：TGC治疗组出现Ap峰GO-G1期细胞明显减少，S期细胞明显增多，与模型对照组比较有显著差异（P〈0．05）。实验组下调相关基因Bcl-2蛋白和c-myc mRNA表达水平。TGC组电镜可见细胞内膜结构完好，染色质边集，细胞核形成核带和核突，凋亡细胞数目较多，有新月形或花环状（凋亡小体形成）。结论：TGC诱导肿瘤细胞凋亡，其机制可能与下调Bcl-2和c-myc mRNA表达水平密切相关。     

IL-13对小鼠哮喘模型气道黏蛋白基因Muc5ac及Bcl-2、Bax表达的作用

目的研究白细胞介素-13(IL-13)处理小鼠支气管哮喘(哮喘)模型前后肺组织黏蛋白基因Muc5ac、凋亡相关蛋白Bcl-2和Bax表达的作用,探讨气道黏液过度分泌的机制.方法45只雄性BALB/c小鼠随机分为对照组、哮喘组和IL-13组,每组15只.用逆转录-聚合酶链反应(RT-PCR)方法和免疫组化法分别检测Muc5acmRNA、Muc5ac蛋白、Bcl-2蛋白以及Bax蛋白在肺组织的表达.结果哮喘组和对照组肺组织Muc5acmRNA分别为(0.1552±0.0057)和(0.0633±0.0013),Muc5ac蛋白分别为(0.8849±0.0257)和(0.1166±0.0064),两组比较差异均有统计学意义(P<0.01);IL-13组肺组织Muc5acmRNA和蛋白分别为(0.2807±0.0027)和(1.6138±0.0483),与哮喘组、对照组比较差异也均有统计学意义(P均<0.01).与对照组Bcl-2蛋白(0.3279±0.0136)、Bax蛋白(1.7284±0.0263)相比,哮喘组分别增加和降低(分别为0.8383±0.0310和0.8987±0.0106),两组差异均有统计学意义(P均<0.01);IL-13处理后可分别促进Bcl-2和Bax蛋白增加和降低(分别为1.6934±0.0229和0.3522±0.0152),其和哮喘组的差异均有统计学意义(P均<0.01);哮喘组和IL-13组小鼠肺组织Muc5acmRNA、蛋白表达与Bcl-2蛋白表达均呈直线正相关(P均<0.05),而与Bax蛋白表达则均呈直线负相关(P均<0.05).结论IL-13是引起哮喘气道黏液过度分泌的重要细胞因子,它可能通过改变Bcl-2和Bax的表达导致了上述病变.     

Attenuation of ischemia and/or reperfusion injury during myocardial infarction using mild hypothermia in rats: an immunohistochemical study of Bcl-2, Bax, Bak and TUNEL

The aim of the present study was to determine the beneficial effect of mild hypothermia during ischemia and/or reperfusion injury in myocardial infarction. Sprague-Dawley rats (400 +/- 20 g) were subjected to 30 min occlusion of the left coronary artery followed by 24 h reperfusion. Rats were divided into normothermic (NT; 37 degrees C) and hypothermic (HT; 34 degrees C) groups. In the HT group hypothermia was maintained during coronary occlusion and continued for 30 min following reperfusion. Histological analysis revealed dead cardiomyocytes and polymorphonuclear neutrophil infiltration after 24 h. Myocardial infarction, measured using an image analyzer, showed that the percentage area of infarction was significantly decreased in the HT group. Immunohistochemical analysis was carried out using antibodies against Bcl-2, Bax and Bak. DNA fragments were labeled in situ using the 3'-OH end-labeling method (TUNEL). In the HT group Bcl-2 was induced in many myocytes, whereas Bax and Bak were induced in only a few myocytes. A higher number of TUNEL-positive cells were recorded in the NT group than in the HT group, but these were more thinly scattered in the HT group. The expression pattern revealed that many myocytes could survive at the border zone in the HT group; in contrast, few myocytes in the NT group were able to survive. Our results suggest that mild hypothermia selectively interferes with, and mitigates, reperfusion injury.     

Genetic analysis of immune dysfunction in non-obese diabetic (NOD) mice: Mapping of a susceptibility locus close to the Bcl-2 gene correlates with increased resistance of NOD T cells to apoptosis induction

The non-obese diábetic (NOD) mouse strain provides a remarkable model for investigating the mechanisms of autoimmunity. Independent genetic analyses of this model have previously shown that chromosome 1-linked loci were involved in the control of periinsulitis and sialitis on the one hand and of insulitis and diabetes on the other hand. In the present work, analysis of a [NOD × (NOD × C57BL/6)F1] backcross progeny allowed us to clearly dissociate two genetic regions: one was associated with periinsulitis and mapped to the middle region of chromosome 1, in the vicinity of the Bcl-2 gene; the other was associated with insulitis and mapped to the proximal part of the chromosome. Three intermediate markers D1Mit18, D1Mit5 and D1Mit19 covering at least 25 centiMorgans between these two regions, were associated with neither periinsulitis nor insulitis. The role of the Bcl-2-linked region in the immune anomalies of NOD mice was further investigated in a (NOD × C57BL/6)F2 cross where the Bcl-2^nod haplotype was linked to elevated serum levels of IgG (p 0.0005). The middle region of chromosome 1 is, therefore, involved in the control of three phenotypes, including periinsulitis, sialitis and hyperIgG, pointing to Bcl-2 as a good candidate for a cause of the NOD mouse disease. Consistent with the anti-apoptotic function of the Bcl-2 gene product, activated T lymphocytes from NOD mice showed a markedly increased resistance to induction of apoptosis following deprivation of interleukin-2 when compared to those from non-autoimmune strains. After the recent observation of the Fas gene alterations in the lpr and lpr^cg mutations, these findings indicate that deregulation of lymphoid cell apoptosis may be a general pathogenetic mechanism in autoimmune diseases.     

Estrogen modulates Bcl-2 family protein expression in the sexually dimorphic nucleus of the preoptic area of postnatal rats

In the sexually dimorphic nucleus of the preoptic area (SDN-POA) of postnatal rats, apoptotic cells are detected more frequently in females than males. This sex difference is under the influence of aromatized androgen. We have reported that there are sex differences in the levels of Bcl-2 (femalemale) in the central division of the medial preoptic nucleus (MPNc), a significant component of the SDN-POA, followed by a sex difference in induction of apoptosis via caspase-3 activation (female>male). In the present study, we examined effects of estradiol benzoate (EB) on expression of Bcl-2 and Bax in the MPNc. Female rats were subcutaneously injected with EB (25 or 50 microg per head) on postnatal day 5. MPNc and caudate putamen (CP) tissues were obtained from EB-treated female and male rats on postnatal day 6. Protein levels of Bcl-2 and Bax were determined by Western blotting. In the MPNc of female rats, EB at a dose of 50 microg/head but not 25 microg/head significantly increased Bcl-2 protein level and decreased Bax protein level. The levels of Bcl-2 and Bax of female rats treated with 50 microg of EB were comparable to those of male rats. However, the protein levels of Bcl-2 and Bax in the CP did not change with EB treatment. These results suggest that estrogen up-regulates Bcl-2 expression and down-regulates Bax expression in the MPNc of postnatal rats. Effects of estrogen on the Bcl-2 family are presumably responsible for sex difference in postnatal apoptosis of the SDN-POA.     

The use of Bcl-2 and PTHLH immunohistochemistry in the diagnosis of peripheral chondrosarcoma in a clinicopathological setting

Distinguishing osteochondroma from low-grade secondary peripheral chondrosarcoma can be difficult. In osteochondroma, growth-signalling pathways are thought to be downregulated through exostosin (EXT) inactivation. A previous pilot study focusing on expression of putative EXT downstream effectors indicated that progression of osteochondroma towards grade I chondrosarcoma was characterised by upregulation of Bcl-2 and parathyroid hormone-like hormone (PTHLH). We investigated their use as diagnostic markers in a large nationwide series of 71 osteochondromas and 34 chondrosarcomas. Bcl-2 immunohistochemistry proved to be a valuable diagnostic tool: scoring negative in 95% (specificity) of the osteochondromas and positive in 57% (sensitivity) of the chondrosarcomas, reaching a positive predictive value of 84% and negative predictive value of 82%. Positivity was not related to age, hereditary status, gender or thickness of the cartilage cap. Presence of internal controls and verification using mRNA in situ hybridisation strengthened the reliability of the immunohistochemical staining. PTHLH showed more variable staining, being positive in osteochondromas from females or adolescent males, suggesting age- and gender-dependent expression. Thus, in cases where the distinction between osteochondroma and chondrosarcoma is difficult, Bcl-2 is a valuable diagnostic marker for malignancy, regardless of tumour size, patient gender or age, and this can be extended with PTHLH for non-adolescent male patients.     

Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in a case of ameloblastic fibrosarcoma

Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only 68 cases reported in the English literature up to 2009. It is composed of a benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the lesion, little is known about its molecular pathogenesis; therefore, in the current study, we sought to evaluate the immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained with its benign counterpart, as well as to report a new case of this rare entity affecting a 19-year-old female patient. The results obtained revealed that all the proteins evaluated were overexpressed in the malignant mesenchymal portion of AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative factors such as Ki67 and proliferative cell nuclear antigen, in association to histopathologic features, may be useful markers for identifying the malignancy and that, despite the lack of molecular analysis in the case reported, Bcl-2 alteration may play a role in AFS pathogenesis.     

Analysis of the expression of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disorders

To investigate the expression of apoptosis-related protein (Fas, FasL, and Bcl-2) in the pathogenesis of autoimmune thyroid disorders (ATDs), immunohistochemical staining was performed on 20 Hashimoto‘s thyroiditis (HT), 20 Graves‘ disease (GD), and 20 thyroid follicular adenoma (TFA, as control). All the cases expressed Fas, mainly on the cell surface and cytoplasm. FasL was found in 17 cases of the TFA. Bcl-2 was detected in 15 cases of HT, 19 of GD and 17 of TFA. In T FA, a moderate Fas expression and a minimal or no FasL expression was detected on follicular cells. In HT, the follicles adjacent to infiltrating lymphocytes showed increased levels of Fas and FasL expression. A weaker staining of Fas and FasL was exhibited on infiltrating lymphocytes than on thyrocytes. In a comparison of GD with HT, thyrocytes and lymphocytes showed similar Fas staining, but for FasL the staining was rather weaker in HT. The expression of Bcl-2 was nearly identical in GD and TFA, but much weaker on the follicular cells in vicinity of lymphocytes and on the lymphocytes located in germinal centers of HT tissues. The expression of Fas, FasL, Bcl-2 in Hashimoto‘s thyroiditis and Graves‘ disease were almost same. FasL strong expression and Bcl-2 weak expression on the follicles in HT may induce apoptosis. These results provided evidence for expression of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disease. The lymphocytes seem not to be directly engaged in the process v/a their own FasL, but they may provide some cytokines that, in turn, upregulate Fas and/or FasL expression to induce apoptosis.     

Acupuncture protected cerebral multi-infarction rats from memory impairment by regulating the expression of apoptosis related genes Bcl-2 and Bax in hippocampus

Vascular dementia (VaD) is the second most common cause of dementia in the world today. In this paper, we observed the effect of acupuncture on memory impairment, apoptosis and expression of Bcl-2 and Bax in hippocampus of cerebral multi-infarction rats. The results indicated that acupuncture significantly improved memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time in the target quadrant. Meanwhile, based on the observation in hippocampal CA1 region through methods of the terminal deoxynucleotidyl transferase nick end labeling (TUNEL), immunohistochemistry and in situ hybridization, acupuncture decreased the number of apoptotic cells and expression of the proapoptotic Bax gene, on the contrary, it increased expression of the antiapoptotic gene Bcl-2. The result of the research suggested that acupuncture can exert antiapoptotic effect through counter-regulating Bcl-2 and Bax gene expression.     

Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of apoptosis by affecting the Bcl-2/Bax balance in non-small cell lung cancer

Deleted in pancreatic carcinoma locus 4 influences tumorigenesis and tumor progression by various mechanisms, including apoptosis. The aim of this study is to determine whether deleted in pancreatic carcinoma locus 4 participates in apoptosis in lung cancer and clarify its relationship with clinical parameters of non-small cell lung cancer. Immunohistochemical results revealed that the positive rate of deleted in pancreatic carcinoma locus 4 in normal tracheal-bronchial epithelium (89.5%, 17/19) was much higher than that in tumor tissues (63.5%, 33/52) (P < .05) and closely correlated with lymph node metastasis (P < .001). These results were further confirmed by Western blot analysis. Furthermore, deleted in pancreatic carcinoma locus 4 overexpression was inversely associated with Bcl-2 immunostaining (P < .01), and the apoptosis index in deleted in pancreatic carcinoma locus 4-positive carcinomas (8.65 +/- 1.46) was much higher than that in deleted in pancreatic carcinoma locus 4-negative carcinomas (2.12 +/- 0.04) (P < .05). The results of deleted in pancreatic carcinoma locus 4 small interfering RNA in A549 cells also showed that deleted in pancreatic carcinoma locus 4 could inhibit cell proliferation, decrease Bcl-2 mRNA and protein expression, and increase Bax messenger RNA and protein expression. These findings indicated that Deleted in pancreatic carcinoma locus 4 might be an important biomarker for malignant transformation and be involved in inducing apoptosis by modulating Bcl-2/Bax balance.     

bFGF对卵巢癌CAOV3细胞Bcl-2、Bcl-xl、Bax、Bad表达的影响

目的研究bFGF调控卵巢癌CAOV3凋亡的信号通路及对Bcl-2、Bcl-xl、Bax、Bad表达的影响。方法无血清饥饿诱导细胞凋亡。分为饥饿对照、bFGF、bFGF PD98059、bFGF Wortmannin组。流式细胞术、DNA Ladder检测细胞凋亡;Western印迹法检测ERK、PKB、Bad活性以及Bcl-2、Bax表达,RT- PCR检测Bcl-2、Bcl-xl mRNA变化。结果bFGF促进p-ERK、p-PKB、p-Bad、Bcl-2表达,抑制Bax表达及饥饿诱导的细胞凋亡。激酶抑制剂PD98059可抑制bFGF对ERK、Bcl-2、Bax的调节作用,Wortmannin可抑制bFGF对PKB、Bad、Bax的调控作用,二者均可阻断bFGF对凋亡的抑制作用。bFGF对Bcl-xl表达无影响。结论bFGF可能通过激活MEK/ERK、P13K/PKB信号途径通路调节Bcl-2、Bax、Bad表达,抑制饥饿诱导的卵巢癌CAOV3细胞凋亡。