Methylseleninic Acid on The Apoptosis Induction and Invasion Inhibition in Human High-Meta-static Large Cell Lung Cancer Cell Line L9981

Background and Objective Lung cancer, which has been proved to have fastest increasing rate of morbidity and mortality, appears to be one of the most dangerous malignant tumor that is     

Mechanisms of Growth Inhibition of Human Lung Cancer Cell Line, PC-9, by Tea Polyphenols

(–)-Epigallocatechin gallate (EGCG), the main constituent of green tea, and green tea extract show growth inhibition of various cancer cell lines, such as lung, mammary, and stomach. We studied how tea polyphenols induce growth inhibition of cancer cells. Since green tea extract contains various tea polyphenols, such as EGCG, (–)-epigallocatechin (EGC), (–)-epicatechin gallate (ECG), and (–)-epicatechin (EC), the inhibitory potential of each tea polyphenol on the growth of a human lung cancer cell line, PC-9 cells, was first examined. EGC and ECG inhibited the growth of PC-9 cells as potently as did EGCG, but EC did not show significant growth inhibition. The mechanism of growth inhibition by EGCG was studied in relation to cell cycle regulation. Flow cytometric analysis revealed that treatment with 50 μM and 100 μM EGCG increased the percentages of cells in the G₂-M phase from 13.8% to 15.6% and 24.1%, respectively. The DNA histogram after treatment with 100 μM EGCG was similar to that after treatment with genistein, suggesting that EGCG induces G₂-M arrest in PC-9 cells. Moreover, we found by microautoradiography that [³H]EGCG was incorporated into the cytosol, as well as the nuclei. These results provide new insights into the mechanisms of action of EGCG and green tea extract as cancer-preventive agents in humans.     

腺病毒介导的IL-24对人大细胞肺癌NCI-H460细胞的体外抑制效应

目的研究腺病毒介导的IL-24基因表达对NCI-H460肺癌细胞抑癌增效作用及分子机制。方法将Ad-IL-24重组腺病毒感染NCI-H460细胞。以Western blot法鉴定IL-24基因在NCI-H460细胞中的表达;MTT法检测重组腺病毒对NCI-H460细胞的生长抑制作用;经Annexin-V-PE/7-AAD染色后流式细胞术（FCM）检测细胞凋亡率变化;RT-PCR检测NCI-H460细胞中bax、caspase-3、bcl-2、survivin等因子的表达。结果腺病毒介导的IL-24基因在NCI-H460细胞中能够有效表达;Ad-IL-24组对NCI-H460细胞的生长具有明显的抑制作用, Ad-IL-24能够上调bax、caspase-3等因子的表达,下调bcl-2、survivin等因子的表达,诱导细胞凋亡。结论腺病毒介导的IL-24 基因在体外可明显抑制人肺癌细胞NCI-H460的生长,诱导其凋亡,其分子机制可能与上调bax、caspase-3等促凋亡因子的表达,下调bcl-2、survivin等凋亡抑制因子的表达有关。     

Comparative Evaluation of Antiproliferative Activity and Induction of Apoptosis by some Fluoroquinolones on a Human Non-small Cell Lung Cancer Cell Line in Culture

Lung cancer is the leading cause of cancer- related death in the world today. Since the effective management of ‍drug resistant lung cancer, and particularly non-small cell lung carcinomas is a major problem, attempts need to be ‍made to identify new potential anticancer drugs that can kill non-small cell lung cancer cells efficiently. In the ‍present study, a human non-small cell lung carcinoma NCI-H460 cell line was used to evaluate the antiproliferative ‍activity of Fluoroquinolones like Enoxacin, Norfloxacin, Ciprofloxacin and Levofloxacin. As determined by ‍Sulphorodhamine B assay (SRB assay), all Fluoroquinolones caused cellular growth inhibition in a concentration ‍and time-dependent manner. Enoxacin was found to be the most effective Fluoroquinolone followed by Norfloxacin, ‍Ciprofloxacin and Levofloxacin. Growth inhibitory effects were also found to be independent of the concentrations ‍of serum growth factors in culture medium or variation of initial cell seeding density and proved to be irreversible in ‍nature. Appearance of rounded cells with altered morphology and cell surface blebbing indicated cell killing by ‍apoptosis. Cell shrinkage, nuclear condensation & fragmentation, and cytoplasmic blebbing as indicated by MGG ‍staining confirmed this to be the case. Thus, this investigation clearly demonstrated that the NCI-H460 human nonsmall ‍cell lung carcinoma cell line is highly sensitive to Fluoroquinolone treatment. The Fluoroquinolones used in ‍this study which are clinically used as antibacterial agents, can also inhibit tumor cell growth suggesting their potential ‍use in a strategy for cancer treatment which might help in controlling cancer.     

石蒜碱诱导肺癌NCI-H460细胞凋亡作用及其机制

目的 通过研究石蒜碱在体外对人肺癌NCI-H460细胞增殖抑制和诱导凋亡的作用,探讨石蒜碱抗肿瘤机制。方法 MTT法检测石蒜碱对NCI-H460细胞增殖的抑制作用,流式细胞术检测NCI-H460细胞的凋亡率,比色法检测凋亡因子相关因子Caspase 3活性。结果 石蒜碱能够有效抑制肺癌NCI-H460细胞增殖,IC₅₀为（5.79±0.11）μmol/L,对NCI-H460细胞的凋亡具有诱导效应,可增强肺癌Caspase 3的活性。结论 石蒜碱在体外能有效地抑制NCI-H460细胞增殖并促进其凋亡,其机制可能与激活Caspase 3的表达从而诱导肿瘤细胞凋亡有关。     

Effect of Tea Polyphenols on the Adhesion of Highly Metastatic Human Lung Carcinoma Cell Lines to Endothelial Cells in Vitro

Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis.For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted toinvestigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelialcells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PGcells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopydouble fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression ofCD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantlyblocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influencedCD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusion: The data indicatedthat the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54.The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibitingadhesion molecule expression to block cancer cell adhesion.     

The Difference of the Copy Number Variation and Loss of Heterozygosity of Human Lung Large Cell Cancer Cell Line with Different Metastatic Potential

Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by disrupting     

尼美舒利对人小细胞肺癌细胞株NCL-H446增殖的抑制作用

目的研究尼美舒利对人小细胞肺癌细胞株NCL-H446增殖的抑制作用,为临床治疗提供实验室依据。方法常规培养人小细胞肺癌细胞株NCL-H446,MTT法检测尼美舒利的细胞毒性作用;倒置显微镜与Hoechst33258荧光染色观察细胞形态学变化;流式细胞术(FCM)分析细胞凋亡率。结果MTT显示尼美舒利呈剂量与时间依赖性抑制人小细胞肺癌细胞株NCL-H446的增殖;倒置显微镜下可见细胞变小、变圆、皱缩、部分细胞脱落飘浮于培养基中。荧光显微镜下可见细胞核染色质致密浓缩、荧光强度增强、染色质边集、核破碎,凋亡小体形成等。FCM检测结果表明尼美舒利既可诱导NCL-H446细胞凋亡,又可引起坏死,400μmol/L的尼美舒利作用细胞24h后,细胞早期凋亡率为7.65%,晚期凋亡率为29.76%,细胞坏死占23.9%。结论尼美舒利对体外培养的人小细胞肺癌细胞株NCL-H446有较显著的抑制作用,该作用与诱导细胞凋亡与坏死有关。     

全反式维甲酸对人膀胱癌细胞株T24生长 抑制和凋亡诱导作用的实验研究

 目的　探讨全反式维甲酸(ATRA)对人膀胱癌细胞T24的生长抑制和凋亡诱导作用。方法　应用细胞和分子生物学技术检测不同浓度ATRA对T24细胞生长和凋亡的影响。结果　3×10-5M～3×10-7M ATRA可显著抑制T24细胞增殖。用3×10-5M和3×10-6M ATRA作用细胞6天出现典型凋亡特征;3×10-5M、3×10-6M组及对照组的细胞凋亡率分别为20.16%、15.31%和1.49%;DNA琼脂糖凝胶电泳呈现凋亡特征性的DNA梯形带。结论　ATRA对人膀胱癌细胞T24有剂量生长抑制作用,且可成功地诱导人膀胱癌细胞T24发生凋亡。     

The Difference of Gene Expression Prof ile in Human Large Cell Lung Cancer Cell Lines with Different Metastatic Potential

Background and Objective Lung cancer is the most lethal malignangy that threatens human heath and lives nowadays in the world, and meanwhile is also the one with worst clinical     

Alteration of Gene Expression Profile and Signal Pathway Induced by Methylseleninic Acid in Human Lung Cancer Cell Lines

Objective and Methods Lung cancer has a fastest growing rate of morbidity and mortality among malignant tumors and poses a great threat to the human health. Chemotherapy, as one of     

热疗对人宫颈癌Hela细胞凋亡的影响

目的:观察不同加温温度对人宫颈癌Hela细胞凋亡的影响.方法:人宫颈癌Hela细胞株常规方法培养,采用水浴加热法(温度为41℃、42.5℃、43.5℃、)对细胞进行加温处理,处理后继续培养24h.用流式细胞仪检测细胞凋亡,单细胞凝胶电泳(single cell gel electrophoresis,SCGE)法检测DNA受损状态.结果:随着温度的增加细胞凋亡率增加,42.5℃、43.5℃加温1h后细胞凋亡率最高分别为30.7%和34.6,坏死细胞分别为13.2%和29.6%.单细胞凝胶电泳发现42.5℃加温1h后40.0%的细胞有DNA损伤,43.5℃加温1h后80.0%以上的细胞DNA损伤,而41℃加温处理1h后仅有20.0%细胞DNA受损.结论:单独加温处理1h可诱导细胞凋亡,并导致细胞DNA损伤.     

茶多酚诱导膀胱癌细胞凋亡及上调PTEN、E-Cadherin表达的研究

目的 :探讨茶多酚抑制膀胱癌细胞生长的可能分子机制。方法 :采用MTT法和流式细胞术 ,观察膀胱癌细胞系 (T2 4及SCaBER)经不同浓度的茶多酚处理后对细胞生长以及PTEN、E cadherin蛋白表达的影响。结果 :茶多酚以剂量依赖的方式抑制膀胱癌细胞的生长 ,加入 0、5 0、10 0、2 0 0、4 0 0 μg·ml-1茶多酚的T2 4细胞和SCaBER细胞抑制率分别为 0 %、11 2 %、33 4 %、36 9%、6 7 5 %和 0 %、16 5 %、19 1%、30 3%、31 4 %。流式细胞仪直方图上可见亚二倍体峰 ,癌细胞出现凋亡 ,凋亡率分别为 6 8%、2 5 1%、2 8 6 %、36 6 %、4 1 1%和 2 1 4、2 7 2 %、2 8 5 %、36 8%、4 7 7% ;同时 ,随茶多酚作用浓度的增加 ,出现G1/S阻滞细胞逐渐增多 ,细胞分裂增殖指数 (PI)降低 ;而细胞PTEN蛋白表达水平由 (37 6 6± 0 4 9)、(38 2 8± 0 6 1)逐渐增加至(16 3 92± 3 36 )、(177 36± 10 79) ,E cadherin蛋白表达水平由 (37 5 2± 1 14 )、(38 5 9± 4 2 4 )逐渐增加至 (12 1 86± 1 5 0 ,15 3 5 8± 2 5 1) (P <0 0 1,P <0 0 1)。结论 :茶多酚对T2 4及SCaBER细胞生长具有抑制作用 ,其机制可能是通过上调PTEN蛋白表达影响细胞周期和诱导细胞凋亡。PTEN、E cadherin蛋白表达水平的上调可能具有逆转细胞恶性生     

茶多酚对膀胱癌细胞株T24和SCaBER体外生长抑制的实验研究

目的　研究茶多酚对膀胱癌细胞株生长的抑制作用及其可能的分子机制。方法　采用MTT法和流式细胞术 ,分析膀胱癌细胞株 (T2 4及SCaBER )经不同浓度的的茶多酚作用前后 ,细胞生长抑制率、细胞凋亡率、细胞周期以及细胞PTEN蛋白表达变化的影响。结果　培养液中加入 0、5 0、10 0、2 0 0、40 0 μg·ml-1茶多酚 ,T2 4细胞和SCaBER细胞的生长抑制率分别为 0、11.2 %、3 3 .4%、3 6.9%、67.5 %和 0、16.5 %、19.1%、3 0 .3 %、3 1.4%。流式细胞仪直方图上见亚二倍体峰 ,2株癌细胞均出现凋亡 ,凋亡率分别为 6.8%、2 5 .1%、2 8.6%、3 6.6%、41.1%和 2 1.4%、2 7.2 %、2 8.5 %、3 6.8%、47.7% ;同时 ,随茶多酚作用浓度的提高 ,阻滞于G1期的 2株癌细胞均明显增加 ,细胞分裂增殖指数 (PI)均降低 ;而细胞PTEN蛋白表达水平分别由 ( 3 7.66± 0 .49)、( 3 8.2 8± 0 .61) (TP ,0 μg·ml-1)增加至 ( 163 .92± 3 .3 6)、( 177.3 6± 10 .79) (TP ,40 0 μg·ml-1) (P均 <0 .0 1)。结论　茶多酚对T2 4及SCaBER细胞生长具有抑制作用 ,其机制之一可能是通过上调PTEN蛋白表达阻滞细胞由G1期进入S期和诱导细胞凋亡。TP抑制T2 4细胞株生长较SCaBER细胞敏感     

Caspase活化的细胞凋亡在非小细胞肺癌组织中的表达

目的：观察非小细胞肺癌（NSCLC）组织中Caspase活化的癌细胞凋亡与临床病理特征的关系。方法：对手术切的NSCLC组织标本50例（其中鳞癌24例，腺癌26例），采用Caspase特异的单克隆抗体－M30 CytoDEATH免疫组化染色方法 显示凋亡细胞，计算凋亡指数（AI），结果：28．0％（14／50）的肺癌组织标中中可见不同程度的M30表达，其中肺鳞癌组织的M30阳性表达率（41．7％）明显高于肺腺癌（15．3％），有显著性差异（P＜05），肺鳞癌组织的AI亦高于腺癌，有显著性差异（P＜0．05），低分化NSCLC 组织的AI高于中，高分化的NSCLC组织，有显著性差异（P＜0．05），低分化鳞癌组织的AI明显高于中高分化的鳞癌，有显著性差异（P＜0．05），M30的表达与其它临床病理学特征无相关性。结论：非小细胞肺癌组织中存在Caspase活化的自发性癌细胞凋亡控制，且Caspase的表达与组织类型及组织分化程度有关。     

法尼基转移酶抑制剂ManumyCin诱导HepG2细胞凋亡的研究

目的:研究法尼基转移酶抑制剂Manumycin对人肝癌HepG2细胞的抗肿瘤作用,并探讨其诱导凋亡的分子机制。方法:采用MTT(Methythiazolyltetrazolium)法观察法尼基转移酶抑制剂Manumycin对肝癌细胞株HepG2细胞增殖的抑制作用,荧光显微镜、DNA凝胶电泳、流式细胞术等技术检测细胞凋亡,应用Westernblot方法检测bcl-2、p53、bax的蛋白水平变化。结果:法尼基转移酶抑制剂Manumycin能明显抑制HepG2细胞的生长且呈浓度依赖性,其IC50为(17.65±0.58)μmol/L。荧光显微镜检查显示Manumycin处理的HepG2细胞DAPI染色后,细胞核内可见浓染致密的颗粒荧光,典型细胞可见新月型改变,固缩或片段化的核。DNA凝胶电泳可见典型的DNA梯形带。流式细胞DNA直方图上出现典型的亚二倍体“凋亡峰”,细胞凋亡与Manumycin作用的时间和浓度相关。Manumycin能时间依赖性地诱导HepG2细胞发生G2/M期阻滞。Manumycin处理HepG2细胞后,Westernblot检测结果显示p53蛋白表达明显增加,而bcl-2蛋白和bax蛋白表达无明显变化。结论:法尼基转移酶抑制剂Manumycin对人肝癌细胞株HepG2有强烈的细胞毒作用,其分子机制可能是诱导HepG2细胞凋亡。Manumycin诱导HepG2细胞凋亡与bcl-2蛋白和bax蛋白表达水平无关,而p53蛋白表达水平的上调可能在此过程中起了一定     

Black Tea Polyphenols Restrict Benzopyrene-induced Mouse Lung Cancer Progression through Inhibition of Cox-2 and Induction of Caspase-3 Expression

Lung cancer is one of the leading causes of cancer related death in most developed and many developing countriesof the world. Due to lack of validated screening methods and poor prognosis, treatment of lung cancer has notimproved significantly over the last two decades. Therefore the risk of the disease needs to be minimized by preventivemeasures. One approach for lung cancer prevention envisages reversal or restriction of precancerous lesions bychemopreventive intervention. It demands a deeper understanding of the pathogenesis of the disease and identificationof the ideal point of intervention. In the present investigation, tea components, epigallocatechin gallate (EGCG) andtheaflavins (TF) were assessed for their chemopreventive potential when administered in the post initiation phase oflung carcinogenesis in an experimental mouse model. Histopathological changes in lungs of mice administeredbenzo(a)pyrene (BP) were followed serially and correlated with the expression of Cox-2, caspase-3 and caspase-7,which play key roles in histopathogenesis of neoplasia. The observations strongly indicate that both EGCG and TFcan influence the expression of these genes to modulate the process of carcinogenesis, resulting in delayed onset andlowered incidence of pre-invasive lung lesions.     

非小细胞肺癌DNA含量和细胞凋亡的相关性研究

目的：探讨非小细胞肺癌（ＮＳＣＬＣ）ＤＮＡ含量和细胞凋亡的关系。方法应用流式细胞技术检测３５例ＮＳＣＬＣ和５例正常肺组织的ＤＮＡ含量,凋亡率,计算ＤＮＡ指数、增殖指数。结果：ＮＳＣＬＣ的ＤＮＡ异倍体再现率为７１．４３％,ＤＮＡ指数、增殖指数显著高于正常肺组织,异倍体尤其明显;ＮＳＣＬＣ的弊端喜讯发率显著低于正常肺组织,并与ＤＮＡ指数负相关。结论：ＤＮＡ含量增加、增殖活性增强和凋亡减少在ＮＳＣＬＣ具     

Establishment of a Human Small Cell Lung Cancer Cell Line Producing a Large Amount of Anti-diuretic Hormone

A new cancer cell line (Lu-165) producing a large amount of anti-diuretic hormone (ADH, 2.8 μg/g protein) was established from a 50-year-old small cell lung cancer patient presenting with a syndrome of inappropriate anti-diuretic hormone secretion. These cells grew well in serum-supplemented medium and during more than 100 passages they continued producing a large amount of this hormone. This cell line will be a useful tool for studies of the biochemistry and pathology of ADH-producing cancer.     

丁酸钠诱导高转移人肺癌细胞恶性表型逆转和抑制侵袭作用的研究

 本文作者选用丁酸钠处理克隆化高转移人肺巨细胞癌（PGCL3）细胞，发现肿瘤细胞在形态、增殖速度、分裂指数、软琼脂集落形成能力和凝集反应等方面均出现向正常细胞表型逆转，证明丁酸钠具有抑制PGCL3细胞增殖及诱导分化的作用。我们还进行了反映肿瘤细胞浸润和转移能力的粘附、运动和降解侵袭实验，结果显示丁酸钠对PGCL3细胞的上述三种能力都有明显的抑制作用，表明丁酸钠在诱导PGCL3细胞向成熟方向分化的同时，还使PGCL3细胞的侵袭能力减弱。