PPARgamma-dependent effects of conjugated linoleic acid on the human glioblastoma cell line (ADF)

Conjugated linoleic acid (CLA) has been shown to exert beneficial effects against carcinogenesis, atherosclerosis and diabetes. It has been demonstrated that CLA modulates lipid metabolism through the activation of peroxisome proliferator-activated receptors (PPARs). The PPAR family comprises 3 closely related gene products, PPAR alpha, beta/delta and gamma, differing for tissue distribution, developmental expression and ligand specificity. It has also been demonstrated that activated PPARgamma results in growth inhibition and differentiation of transformed cells. These observations stimulated a great interest toward PPARgamma ligands as potential anticancer drugs to be used in a differentiation therapy. Glioblastomas are the most commonly diagnosed primary tumors of the brain in humans. The prognosis of patients with high-grade gliomas is poor and only marginally improved by chemotherapy. The aim of this work was to study the effects of CLA and of a specific synthetic PPARgamma ligand on cell growth, differentiation and death of a human glioblastoma cell line as well as on parameters responsible for the metastatic behavior of this tumor. We demonstrate here that CLA and PPARgamma agonist strongly inhibit cell growth and proliferation rate and induce apoptosis. Moreover, both treatments decrease cell migration and invasiveness. The results obtained show that CLA acts, directly or indirectly, as a PPARgamma activator, strongly suggesting that this naturally occurring fatty acid may be used as brain antitumor drug and as a chemopreventive agent. Moreover, the gamma-agonist, once experimented and validated on man, may represent a useful coadjuvant in glioblastoma therapy and in the prevention of recurrences.     

n-3多不饱和脂肪酸在食管癌细胞增殖和凋亡中的作用机制探讨

目的:探讨n-3多不饱和脂肪酸的两个活性成分二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)在食管癌细胞增殖和凋亡中的作用。方法:采用 CCK-8法测定不同浓度、不同时间点（培养后 24 h、48 h、72 h）的DHA、EPA对食管癌细胞增殖的影响,用Western-blot法检测DHA、EPA对凋亡相关蛋白表达的影响,并用荧光染色和流式细胞仪检测DHA、EPA对食管癌细胞凋亡的影响。结果:与对照组相比,DHA和EPA均能够抑制食管癌细胞的增殖并具浓度依赖性,但无时间依赖性。Western-blot 显示DHA、EPA能激活Caspase-3和Bax表达,抑制抗凋亡蛋白Bcl-2表达。DHA和EPA作用24 h后,荧光染色可见部分食管癌细胞呈典型的凋亡形态学改变。流式细胞仪检测结果显示,与对照组比较,DHA和EPA能够诱导食管癌细胞凋亡,且与浓度呈正比。结论:n-3多不饱和脂肪酸能够抑制食管癌细胞的增殖和诱导食管癌细胞的凋亡,调控Caspase-3活性以及 Bcl-2 家族促凋亡蛋白/抗凋亡蛋白之间的平衡来发挥其抑制食管癌细胞增殖和诱导食管癌细胞凋亡的作用。     

p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo

Berberine has been shown to have anti-carcinogenic effects. Since p53 is the most commonly mutated tumor suppressor gene, and a lack of functional p53 is associated with an increased risk of cancer development, we examined the effects of berberine on p53-positive and p53-deficient non-small cell human lung cancer cells in vitro and in vivo. Treatment of A549, which express wild-type p53, and H1299, which are p53-deficient, human lung cancer cells with berberine resulted in inhibition of cell proliferation and an increase in apoptotic cell death; however, A549 cells were more sensitive to the berberine-induced cytotoxic effects than H1299 cells. Further, the treatment of A549 cells with pifithrin-alpha, a specific inhibitor of p53, or transfection of A549 cells with a p53 antisense oligodeoxynucleotide resulted in a reduction in the berberine-induced inhibition of cell proliferation and apoptosis. The berberine-induced apoptosis of both the A549 and H1299 human lung cancer cells was associated with the disruption of mitochondrial membrane potential, reduction in the levels of Bcl-2, Bcl-xl while increase in Bax, Bak, and activation of caspase-3. Treatment of the cells with pan-caspase inhibitor (z-VAD-fmk) or caspase-3 inhibitor (z-DEVD-fmk) inhibited berberine-induced apoptosis, thus suggesting the role of caspase-3. Further, the administration of berberine by oral gavage inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, however, the growth of tumor xenograft of H1299 cells was faster than A549 cells in mice and the chemotherapeutic effect of berberine was more pronounced in the p53-positive-A549 tumor xenograft than p53-deficient-H1299 tumor xenograft.     

胞外环境Ca~(2 )变化诱导人肿瘤细胞凋亡

目的 :观察胞外环境Ca2 变化对人肿瘤细胞的直接诱导凋亡作用。方法 :通过EGTA螯合胞外Ca2 或添加CaCl2 改变胞外环境Ca2 。用PI和Hoechst3334 2荧光双染观察细胞核形态 ,用流式细胞仪检测凋亡百分率。分别借助荧光探针Fluo 3和Rh12 3检测胞内Ca2 和线粒体膜电位 (ΔΨm)变化。用环孢菌素A(CsA)阻断PT孔 ,研究其在凋亡中的作用。结果 :胞外环境Ca2 升高或降低均诱导人胃癌MGC 80 3和喉癌Hep细胞凋亡 ,恢复胞外Ca2 阻断凋亡。随胞外Ca2 变化胞内Ca2 相应升高或降低 ,但线粒体ΔΨm均表现为急剧下降。CsA对MGC 80 3细胞凋亡无明显抑制作用 ,轻微促进Hep细胞凋亡。结论 :胞外环境Ca2 变化引起胞内Ca2 相应变化和线粒体ΔΨm下降并通过PT孔非依赖性途径诱导肿瘤细胞凋亡。     

New cell lines of human breast cancer origin

Summary Established human mammary tumor cell lines constitute an important tool in the study of breast cancer. The aim of this work was to isolate and characterize two new mammary tumor cell lines, JCK and GCS, which were obtained from the pleural effusion and ascitic fluid, respectively, from two breast cancer patients. Both cell lines had some properties of transformed cells, namely immortalization and growth in soft agar. The carcinoma cells presented epithelial morphology shown by light and electron microscopy, and antigenic properties shown by different tumor markers such as a cytokeratin cocktail, carcinoembryonic antigen, epithelial membrane antigen, and human milk fat globule membrane antigen. A significant increase was also found (P>0.05) in cell growth and³H-thymidine incorporation into DNA in the JCK and GCS cell lines in the presence of 17 estradiol at concentrations of 10^–9 and 10^–7 M, respectively, after 5 days in culture. These cells presented estradiol receptor levels which were similar in the biopsies and the resulting cell lines. The aromatase activity was also similar in the JCK cell line and the original patient biopsy. However, there was a considerably higher aromatase activity in the GCS cell line than in the biopsy specimen. Southern hybridizations with theneu oncogene showed an additional 12 kb fragment in both cell lines, as also seen in patients with breast cancer. We conclude from these studies that thisin vitro system may provide us with a way to study metastatic cells and improve clinical management of breast cancer patients.     

Influence of n-3 fatty acids on the growth of human breast cancer cellsin vitro: Relationship to peroxides and Vitamin-E

Epidemiological studies suggest a causal relationship of dietary polyunsaturated fatty acids (PUFA's) with the morbidity and mortality from breast cancer. In order to reveal possible underlying mechanisms of these findings, we studied the influence of n-3 and n-6 PUFA's in comparison to oleic acid on the proliferation of well characterized estrogen dependent (MCF-7, ZR-75, T-47-D) and estrogen independent (MDA-MB-231, HBL-100) breast cancer cells in culture. The cell growth inhibitory effect was related to the formation of lipid peroxidation products. Normal human skin fibroblasts served as a control. In fibroblasts, the addition of 20 µg/ml of exogenous fatty acids either had no effect or caused an insignificant increase of proliferation. Similar results were obtained with MCF-7 cells. In all other breast cancer cell types, n-3 long-chain PUFA's, eicosapentaenoic and docosahexaenoic acids, were the most effective fatty acids in arresting the cell growth. Alpha-linolenic and gamma-linolenic acid exerted a variable effect on cell proliferation depending on the cell line investigated. Oleic acid significantly stimulated the proliferation of hormone-independent breast cancer cells while it had no effect on the proliferation of hormone-dependent cells. Viability studies by trypan blue excretion indicated that the arrest in cell growth was not due to major cytotoxic effects.The addition of PUFA's to breast cancer cells caused a significant increase in the formation of conjugated dienes and lipid hydroperoxides in the cellular lipids; their content was significantly correlated with the capacity of arresting cell growth. In contrast, the addition of PUFA's to fibroblasts did not increase lipid hydroperoxide formation. The addition of Vitamin E to cancer cells at a concentration of 10 µM to the PUFA-supplemented medium almost completely restored cell growth.Our data indicate that PUFA's significantly interfere with cell proliferation of breast cancer cellsin vitro due to the formation of oxidation products. In addition to that, there must be other factors involved, most probably related to the differential metabolism of PUFA's in tumor cells. Our findings may have some impact on treatment and prevention of breast cancer.Abbreviations ALA Alpha-Linolenic Acid - GLA Gamma-Linolenic Acid - DHA Docosahexaenoic Acid - EPA Eicosapentaenoic Acid - ER Estrogen Receptor - OA Oleic Acid - PUFA's Polyunsaturated Fatty Acids     

Extracts of Musa basjoo induce growth inhibition and changes in the protein expression of cell cycle control molecules in human colorectal cancer cell lines

Musa basjoo (MB) is a species of the banana plant belonging to the genus Musa that has been used as a folk medicine. However, evidence-based biological activities and the molecular mechanism of action of MB are unknown. Thus, the aim of the present study was to examine whether the crude dried leaf extracts of MB inhibit the growth of colorectal (HT29 and HCT116) and other types (HepG2, MCF-7 and PC-3) of human cancer cell lines. Crude extracts of MB inhibited the growth of cells with IC₅₀ values of 136 µg/ml (acetone extract, HT29), 51 µg/ml (acetone extract, HCT116), 45 µg/ml (acetone extract, HepG2), 40 µg/ml (acetone extract, MCF-7), 29 µg/ml (acetone extract, PC-3), 175 µg/ml (methanol extract, HT29), 137 µg/ml (methanol extract, HCT116), 102 µg/ml (methanol extract, HepG2), 85 µg/ml (methanol extract, MCF-7), and 85 µg/ml (methanol extract, PC-3) in colony formation assays, and 126 µg/ml (acetone extract, HT29), 68 µg/ml (acetone extract, HCT116), 260 µg/ml (methanol extract, HT29), and 216 µg/ml (methanol extract, HCT116) in MTT assays. Thin layer chromatography analysis revealed the potential existence of aromatic compounds in the acetone extract of MB. Flow cytometric analysis indicated that the percentage of cells in G1 increased, and this was associated with a concomitant decrease of cells in the S and/or G2-M phases of the cell cycle. When colorectal cancer cells were treated with acetone extract of MB, there was a marked decrease in the levels of expression of the cyclin D1, cyclin E, cdk2 and cdk4 proteins and a marked increase in the levels of the expression of the p21^CIP1, p27^KIP1, and p53 proteins, but those of apoptosis-associated protein PARP did not change. There was a tendency for acetone extract of MB to inhibit xenograft tumor growth in mice. Collectively, the crude extracts of MB contain active components that exert growth inhibition of human cancer cells. This is the first systematic study of the anticancer activity of MB and may broaden insights into the possible clinical approach of specific herbal medicines.     

Natural killer cells suppress human cutaneous squamous cell carcinoma cancer cell survival and tumor growth

Cutaneous squamous cell carcinoma (CSCC), which develops in response to ultraviolet irradiation exposure, is among the most common cancers. CSCC lesions can be removed by surgical excision, but 4.5% of these cancers reappear as aggressive and therapy-resistant tumors. CSCC tumors display a high mutation burden, and tumor frequency is dramatically increased in immune-suppressed patients, indicating a vital role for the immune system in controlling cancer development. Natural killer cells (NK cells) play a key role in cancer immune surveillance, and recent studies suggest that NK cells from healthy donors can be expanded from peripheral blood for use in therapy. In the present study, we test the ability of ex vivo expanded human NK cells to suppress the CSCC cell cancer phenotype and reduce tumor growth. We expanded human NK cells from multiple healthy donors, in the presence of IL-2, and tested their ability to suppress the CSCC cell cancer phenotype. NK cell treatment produced a dose-dependent reduction in SCC-13 and HaCaT cell spheroid growth and matrigel invasion and induced SCC-13 and HaCaT cell apoptosis as evidenced by increased procaspase 9, procaspase 3, and PARP cleavage. Moreover, two important CSCC cell pro-cancer signaling pathways, YAP1/TAZ/TEAD and MEK1/2-ERK1/2, were markedly reduced. Furthermore, tail-vein injection of NK cells markedly suppressed the growth of SCC-13 xenograft tumors in NSG mice, which was also associated with a reduction in YAP1 and MEK1/2-P levels and enhanced apoptosis. These findings show that NK cell treatment suppresses CSCC cell spheroid formation, invasion, viability, and tumor growth, suggesting NK cell treatment may be a candidate therapy for CSCC.     

Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and growth

BACKGROUND AND OBJECTIVES: PTEN is a candidate tumor suppressor gene in a variety of malignant tumors, including renal cell carcinoma (RCC). PTEN regulates cell cycle progression and cell survival in vivo. However, the role of PTEN alterations and their association with tumor growth and behavior in patients with RCC has not been well established. The aim of our study was to evaluate PTEN expression in RCC and its correlation with clinicopathologic features, cell proliferation, and apoptosis. METHODS: Sixty-seven RCC specimens were examined immunohistochemically with anti-PTEN antibody. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67 antibody. RESULTS: Twenty-one (31.3%) of the 67 RCCs showed reduced PTEN expression. The apoptotic index (AI) varied from 0.2 to 25.5%, and the Ki-67 index (KI) ranged from 1.6 to 69.8%. Reduced PTEN expression correlated with TNM stage (P < 0.05) and nuclear grade (P < 0.05). Tumors with reduced PTEN expression had a significantly higher KI than those with normal PTEN expression (P < 0.01). By univariate analysis, nuclear grade (P = 0.0005), TNM stage (P < 0.0001), AI (P = 0.0220), KI (P = 0.0002), and reduced PTEN expression (P < 0.0001) were associated with shortened survival. However, TNM stage was the only independent prognostic factors by multivariate analysis (P = 0.0007). CONCLUSIONS: Our results suggest that PTEN expression is frequently reduced in advanced RCC. The PTEN gene seems to be important for the growth suppression of RCC, by inhibiting cell proliferation.     

Lectin histochemistry of astrocytic tumors and in vitro characterization of lectin-induced modifications on the proliferation of the SW1088, U373 and U87 human astrocytic cell lines

The role of lectins as biosignalling molecules oras markers of human astrocytic tumors remains relativelyunexplored. The aim of the present work isto investigate (1) whether or not human astrocytictumors express specific glycans, evidenced experimentally by meansof lectin histochemistry, and (2) whether, in turn,these lectins can significantly modulate astrocytic tumor cellproliferation. Using a cell image processor, we thereforebegan by quantitatively measuring the histochemical binding patternof 5 lectins (WGA, PNA, PHA-L, GSA-IA4 andCon A) in 5 astrocytomas, 5 anaplastic astrocytomasand 5 glioblastomas. Secondly, we measured the influenceof these 5 lectins on the proliferation of3 astrocytic tumor cell lines (SW1088, U373 andU87) growing in vitro as monolayers. Cell proliferationwas assessed by means of the colorimetric MTTassay. The histochemical lectin staining markedly varied intra-and inter-group. However, some constant results were obtained.Indeed, the staining increased markedly from GSA-IA4 andPHA-L through WGA and PNA to Con Ain the three histopathological groups. The assessment ofcell proliferation demonstrated that WGA, Con A andPHA-L very significantly decreased proliferation in the 3astrocytic cell lines in a dose-dependent manner. Astrocytictumor cells in the confluent growth phase wereless sensitive to the WGA, Con A andPHA-L lectin-induced effects than cells in the loggrowth phase. The GSA-IA4 and PNA lectins hadglobally very weak effects on the proliferation ofthe astrocytic tumor cell lines. Increasing the fetalcalf serum from 1% to 10% in theculture media significantly antagonized the WGA-, Con A-and PHA-L-induced cell proliferation decrease in the 3astrocytic cell lines. In conclusion, the present datastrongly suggest that some lectins (including WGA, ConA and PHA-L) significantly influence the proliferation ofastrocytic tumor cells.     

二甲双胍对人肺腺癌A549细胞增殖和凋亡的调控

背景与目的:二甲双胍作为一种胰岛素增敏剂被用于Ⅱ型糖尿病的一线治疗。近来的临床研究发现二甲双胍可降低糖尿病患者的肿瘤发生率,提示它可能具有抗肿瘤的作用。本研究观察二甲双胍对人肺腺癌A549细胞增殖及凋亡的影响,并探讨其可能的机制。方法:二甲双胍干预人肺腺癌A549细胞48h后,采用MTT法检测其对细胞增殖的影响,流式细胞术检测细胞凋亡,实时PCR法检测p53、Bcl-2和Bax mRNA的转录情况。结果:经二甲双胍干预48h后,人肺腺癌A549细胞的增殖受到明显抑制,且该抑制作用呈药物浓度依赖性增加。当二甲双胍浓度为0.5、2和8mmol/L时对细胞生长的抑制率分别为(29±5)%、(68±3)%和(84.1±2.6)%。流式细胞术检测提示中、高浓度(2、8mmol/L)二甲双胍可促进A549细胞凋亡;其中,药物作用48h后,8mmol/L组细胞的早期凋亡率为(2.1±0.5)%,中、晚期凋亡率为(9±4)%,均显著高于对照组。二甲双胍干预后细胞凋亡相关基因p53、Bcl-2和BaxmRNA表达均上调,且Bcl-2/Bax比值下调。结论:二甲双胍能显著抑制人肺腺癌A549细胞增殖,促进细胞凋亡增加;其机制可能与上调细胞凋亡相关基因p53的表达及Bcl-2/Bax比值下降有关。     

塞来昔布对SK-N-SH细胞增殖和凋亡影响的研究

目的:探讨特异性环氧化酶-2(COX-2)抑制剂塞来昔布(celecoxib)对人神经母细胞瘤细胞系SK-N-SH细胞生长的影响及其分子生物学作用机制。方法:不同浓度塞来昔布(12.5、25、50和75μmol/L)用不同时间(24、48和72h)处理SK-N-SH细胞,MTT法检测细胞增殖,DNA ladder法及AO/EB染色法分析细胞凋亡,Western blot检测COX-2、Bcl-2蛋白表达。结果:MTT法显示,12.5、25、50和75μmol/L组在3个时间点对细胞的抑制率分别为(7.38±1.12)%、(10.33±1.97)%和(25.16±5.58)%;(34.46±6.76)%、(30.12±6.71)%和(57.54±3.06)%;(61.85±4.01)%、(50.78±2.85)%和(85.67±2.17)%;(83.85±5.56)%、(90.06±5.71)%和(98.04±4.43)%。组间差异均有统计学意义,P<0.05。结论:塞来昔布抑制SK-N-SH细胞的生长并诱导其凋亡,其机制除了抑制COX-2外还可能与抑制Bcl-2有关,有一定的临床应用价值。     

Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study

Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting. Cohort studies reporting serum fatty acid composition are lacking. We assessed the association of fatty acid composition determined from dietary records and serum with incident cancer of the prostate and any site in a population-based cohort of 2,002 middle-aged Finnish men who were free of cancer at baseline and during the first 4 years of follow-up. During 12.6 years of follow-up, 46 men developed prostate cancer and 151 any cancer. Men with proportions of serum nonesterified [risk ratio (RR) 0.28; 95% confidence intervals (CI) 0.12-0.66] and esterified linoleic acid (RR 0.37; 95% CI = 0.16-0.86) and total polyunsaturated fatty acids (RR 0.30; 95% CI = 0.12-0.71) in the upper third were less than 1/3 as likely to develop prostate cancer during follow-up. Adjustment for possible confounders like socioeconomic status, physical activity, obesity and insulin concentrations did not attenuate the association. Similar but weaker associations with any cancer were found. Dietary linoleic acid intake also tended to be inversely associated with incident prostate cancer (age-adjusted RR for the upper vs. lower third 0.55; 95% CI = 0.26-1.14, p for the trend 0.097). Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers, although it is possible that some of the effect may be mediated by nutrients closely associated with vegetable fats.     

尼美舒利对不同COX-2表达水平的食管鳞癌细胞的抑制作用

目的：比较选择性环氧合酶-2（COX-2）抑制剂尼美舒利对不同COX-2表达水平的食管鳞癌细胞的抑制作用。方法：选取食管鳞癌细胞株EC 109、KYSE 150和TE-1,采用Western blot方法测定COX-2蛋白表达、MTT法检测细胞增殖抑制,流式细胞术检测细胞周期和细胞凋亡,观察尼美舒利对各组细胞的增殖抑制和促凋亡作用。结果：COX-2蛋白在EC 109细胞中呈高表达,KYSE 150细胞中呈中等度表达,TE-1细胞不表达COX-2蛋白。尼美舒利在50μmol/L-400μmol/L浓度区间可抑制EC 109、KYSE 150细胞的增殖（P〈0.05）,并呈剂量依赖性,在400μmol/L时对TE-1细胞有抑制作用。EC 109细胞尼美舒利的IC50值最低,KYSE150次之,TE-1最高。尼美舒利可使EC 109和KYSE 150的细胞周期阻滞于G0/G1期,并诱导细胞凋亡,但对TE-1细胞无上述作用。结论：尼美舒利对表达COX-2的食管鳞癌细胞有较好的增殖抑制和促凋亡作用。     

TMPyP4对肝癌细胞HepG2生长抑制作用的研究

目的 TMPyP4是G-四链体的配体,能够诱导形成G-四链体结构并增强G-四链体结构的稳定性,加强G-四链体作为负调控因子抑制MET基因的表达;G-四链体结构的形成可以选择性的抑制肿瘤细胞增殖.本研究旨在分析TMPyP4对肝癌细胞HepG2生长抑制作用的研究,为MET高表达的肿瘤靶向治疗提供新思路.方法 采用CCK 8方法分析HepG2细胞增殖变化,通过Hoechst 33342细胞核染色和Annexin V-FITC/PI双染流式细胞术分析HepG2细胞凋亡水平,以及利用流式细胞术分析HepG2细胞周期分布的变化.结果 CCK-8分析HepG2细胞增殖显示,与对照组比较,10 μmol/L TMPyP4对HepG2细胞存活率无显著影响,20、50、100和200 μmol/L TMPyP4组HepG2细胞存活率分别为(82.28±1.99)％、(68.88±3.06)％、(55.57±2.76)％和(50.32±5.78)％,F=120.542,P＜0.001,说明高于20 μmol/L的TMPyP4显著抑制细胞增殖;流式细胞术分析细胞凋亡不明显,只有高浓度TMPyP4诱导少量HepG2细胞发生了凋亡,并出现了坏死细胞;100和200 μmol/L TMPyP4的实验组细胞经Hoechst 33342染色,有少数HepG2细胞表现出细胞核固缩、致密,形态不规则,染色不均一,呈现凋亡表现;不同浓度的TMPyP4处理HepG2细胞使G0/G1期细胞增加了20％,S期细胞减少,G2/M期细胞也减少,表示HepG2细胞发生了G0/G1细胞周期阻滞.结论 G-四链体的配体TMPyP4显著抑制了肝癌细胞HepG2的细胞增殖,诱导少量HepG2细胞凋亡,并使HepG2细胞发生了G0/Gl细胞周期阻滞.     

PPARalpha and PP2A are involved in the proapoptotic effect of conjugated linoleic acid on human hepatoma cell line SK-HEP-1

Conjugated linoleic acid (CLA), found in dairy products, in beef and lamb has been demonstrated to possess anticancer properties protecting several tissues from developing cancer. Moreover, it has been shown to modulate apoptosis in several cancer cell lines. The aim of this study was to investigate which signaling transduction pathways were modulated in CLA-induced apoptosis in human hepatoma SK-HEP-1 cells. The cells exposed to CLA were evaluated for PPARalpha, PP2A, pro-apoptotic proteins Bak, Bad and caspases, and anti-apoptotic proteins Bcl-2 and Bcl-X(L). Cells were also treated with okadaic acid, a PP2A inhibitor, or with Wy-14643, a specific PPARalpha agonist. The CLA-induced apoptosis was concomitant to the increase of percentage of cells in the S phase, PPARalpha, PP2A and pro-apoptotic proteins; simultaneously, antiapoptotic proteins decreased. Inhibition of PP2A prevented apoptosis, and PPARalpha agonist showed similar effect as CLA. The increased PP2A could be responsible for the dephosphorylation of Bcl-2 and Bad, permitting apoptotic activity of Bax and Bad. The increase of caspase 8 and 9 suggested that both the intrinsic and extrinsic apoptotic pathways were induced. PP2A was probably increased by PPARalpha, since putative PPRE sequences were found in genes encoding its subunits. In conclusion, CLA induces apoptosis in human hepatoma SK-HEP-1 cells, by increasing PPARalpha, PP2A and pro-apoptotic proteins.     

尼美舒利对不同COX-2表达水平的食管鳞癌细胞的抑制作用

目的:比较选择性环氧合酶-2(COX-2)抑制剂尼美舒利对不同COX-2表达水平的食管鳞癌细胞的抑制作用。方法:选取食管鳞癌细胞株EC 109、KYSE 150和TE-1,采用Western blot方法测定COX-2蛋白表达、MTT法检测细胞增殖抑制,流式细胞术检测细胞周期和细胞凋亡,观察尼美舒利对各组细胞的增殖抑制和促凋亡作用。结果:COX-2蛋白在EC 109细胞中呈高表达,KYSE 150细胞中呈中等度表达,TE-1细胞不表达COX-2蛋白。尼美舒利在50μmol/L-400μmol/L浓度区间可抑制EC 109、KYSE 150细胞的增殖(P<0.05),并呈剂量依赖性,在400μmol/L时对TE-1细胞有抑制作用。EC 109细胞尼美舒利的IC50值最低,KYSE150次之,TE-1最高。尼美舒利可使EC 109和KYSE 150的细胞周期阻滞于G0/G1期,并诱导细胞凋亡,但对TE-1细胞无上述作用。结论:尼美舒利对表达COX-2的食管鳞癌细胞有较好的增殖抑制和促凋亡作用。     

免疫营养在恶性肿瘤治疗中的研究现状及进展

免疫营养在临床营养支持、免疫调节和维护肠道黏膜屏障功能方面发挥着重要作用.近年来,免疫营养越来越受到重视,已成为肿瘤营养治疗的发展方向.本文通过对常用的三种免疫营养素谷氨酰胺(Gln)、ω-3多不饱和脂肪酸(ω-3PUFA)和精氨酸(Arg)与恶性肿瘤的关系进行综述,为临床肿瘤患者营养治疗提供参考.     

吉西他滨抑制骨肉瘤细胞系MG-63增殖和诱导凋亡的实验研究

目的研究吉西他滨对骨肉瘤细胞系MG-63的增殖抑制和凋亡诱导作用。方法利用光镜检测吉西他滨作用后MG-63的形态学变化;MTT法检测吉西他滨对MG-63的增殖抑制;流式细胞仪AnnexinV-FITC法检测细胞凋亡,琼脂糖凝胶电泳检测DNA ladder。结果吉西他滨可明显地抑制MG-63细胞生长,各实验组24、48、72小时抑制率随时间的增加而增加,差异有统计学意义（P〈0.05）,0.1 mg/L及以上浓度的吉西他滨对MG-63骨肉瘤细胞的抑制率可达50%,0.1-100 mg/L的吉西他滨对MG-63的抑制率相似。吉西他滨可诱导MG-63细胞凋亡,在不同浓度吉西他滨（0.1,1.0,10.0,100 mg/L）作用48小时后,MG-63的凋亡率差异无统计学意义（P〉0.05）。并且经琼脂糖凝胶电泳可以显示DNA ladder。结论吉西他滨对骨肉瘤细胞系MG-63具有增殖抑制作用,并且各实验组24、48、72小时抑制率随时间的增加而增加;吉西他滨对骨肉瘤细胞系MG-63具有诱导凋亡作用;0.1-100 mg/L吉西他滨对MG-63的增殖抑制和诱导凋亡作用相似。     

大蒜素诱导肿瘤细胞凋亡的作用

近年来实验研究表明,大蒜素具有抗肿瘤细胞增殖及促肿瘤细胞凋亡的生物学作用。部分实验研究表明大蒜素能抑制肿瘤细胞的生长,如白血病、肝癌、胃癌和卵巢癌细胞等,但目前对其诱导细胞凋亡的机制还不清楚。