Krill oil ameliorates benign prostatic hyperplasia by regulating G1-phase cell cycle arrest and altering signaling pathways and benign prostatic hyperplasia-associated markers

Krill oil(KO)exhibits various biological activities,such as anti-inflammatory and antitumor effects.However,the inhibitory effects of benign prostatic hyperplasia(BPH)in vitro and in vivo have not yet been studied.This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method.KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G0/G1 phase arrest through the modulation of positive and negative regulators in both prostate cell types.KO treatment stimulated phosphorylation of c-Jun N-terminal kinase(JNK)and p38 signaling.In addition,KO changed the expression of BPH-related markers(5α-reductase,androgen receptor,FGF,Bcl-2,and Bax)and the activity of the proliferation-mediated NF-κB binding motif.KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38(si-p38)and JNK(si-JNK).Furthermore,the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model.KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues.Finally,KO-mediated inhibition of prostatic growth was validated by histological analysis.These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo.Thus,KO might be a potential prophylactic or therapeutic agent for patients with BPH.

贝母素乙通过诱导G0/G1期阻滞抑制结肠癌细胞的增殖

目的:探讨贝母素乙对结肠癌HCT116细胞增殖的抑制作用及其分子机制。方法:利用不同浓度的贝母素乙处理人结肠癌细胞HCT116和正常结肠上皮细胞CCD841 CON,通过CCK-8法和结晶紫染色法检测贝母素乙对HCT116和CCD841 CON细胞增殖活力的影响,流式细胞术和WB法检测贝母素乙对HCT116细胞周期及其细胞周期相关蛋白表达的影响。构建HCT116移植瘤裸鼠模型和AOM/DSS结肠癌小鼠模型,观察贝母素乙对小鼠模型肿瘤生长和OS的影响,免疫组化法和WB法检测对移植瘤或肿瘤组织中细胞周期相关蛋白CDK4、CDK6和cyclin D1表达的影响。结果:贝母素乙可显著抑制结肠癌HCT116细胞的增殖能力(P<0.01),诱导HCT116细胞周期G0/G1期阻滞(P<0.01),降低CDK4、CDK6和cyclin D1的蛋白表达水平(均P<0.01)。荷瘤小鼠实验结果显示,贝母素乙(0.75 mg/kg)显著抑制HCT116细胞移植瘤的生长并延长荷瘤裸鼠的OS(P<0.05或P<0.01),降低AOM/DSS模型小鼠的体质量、延长OS、减少癌变肠组织的肿瘤个数和肿瘤体积,下调肿瘤组织中CDK4、CDK6和cyclin D1的蛋白表达(P<0.01或P<0.05)。结论:贝母素乙通过下调CDK4、CDK6和cyclin D1的表达水平,引起细胞周期G0/G1期阻滞,从而抑制结肠癌HCT116细胞的增殖。

Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells

AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines,HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological observation,flow cytometry analysis,Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells,as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner,which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition,G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53,pRb,p27,cyclins D1,D2,E,cyclin-dependent kinase (Cdk) 2,Cdk4,and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option,as a potential anticancer agent,in the treatment of hepatoma.

Intrinsic apoptotic pathway and G2/M cell cycle arrest involved in tubeimoside I-induced EC109 cell death

Objective： Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu （TBM）, a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma （ESCC） for a long term. tubeimoside I （TBMS1） is the main component of TBM, exhibiting great anticancer potential. In this study, we investigated the mechanism of TBMS1 cytotoxic effect on EC109 cells. Methods： Comparative nuclear proteomic approach was applied in the current study and we identified several altered protein spots. Further biochemical studies were carried out to detect the mitochondrial membrane potential, cell cycle and corresponding proteins＇ expression and location. Results： Subcellular proteomic study in the nucleus from EC109 cells revealed that altered proteins were associated with mitochondrial function and cell proliferation. Further biochemical studies showed that TBMSl-induced molecular events were related to mitochondria-induced intrinsic apoptosis and P21-cyclin B 1/cdc2 complex-related G2/M cell cycle arrest. Conclusions： Considering the conventional application of TBM in esophageal cancer, TBMS1 therefore may have a great potential as a chemotherapeutic drug candidate for ESCC.

Ethanol extract of Kalopanax septemlobus leaf inhibits HepG2 human hepatocellular carcinoma cell proliferation via inducing cell cycle arrest at G_1 phase

Objective:To investigate the effects of an ethanol extract of Kalopanax septemlobus(Thunb.)Koidz.leaf(EEKS) on cell proliferation in human hepatocellular carcinoma cells and its mechanisms of action.Methods:Cells were treated with EEKS and subsequently analyzed for cell proliferation and flow cytometry analysis.Expressions of cell cycle regulators were determined by reverse transcriptase polymerase chain reaction analysis and Western blotting,and activation of eyclin-associaled kinases studied using kinase assays.Results:The EEKS suppressed cell proliferation in both HepG2 and Hep3 B cells,but showed a more sensitive anli-proliferative activity in HepG2 cells.Flow cytometry analysis revealed an association between the growth inhibitory effect of EEKS and with G_1 phase cell cycle arrest in HepG2 cells,along with the dephosphorylation of retinoblastoma protein(pRB) and enhanced binding of pRB with the E2 F transcription factor family proteins.Treatment with EEKS also increased the expression of cyclin-dependent kinase(CDK) inhibitors,such as p21WAF1/CIP1 and p27KIP1.without any noticeable changes in G_1 cyclins and CDKs(except for a slight decrease in CDK4).Treatment of HepG2 cells with EEKS also increased the binding of p21 and p27 with CDK4 and CDK6.which was paralleled by a marked decrease in the cyclin D- and cyclin E-associated kinase activities.Conclusions:Overall,our findings suggest that EEKS may be an effective treatment for liver cancer through suppression of cancer cell proliferation via G_1,cell cycle arrest Further studies arc required to identify the active compounds in EEKS.

1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a derivative of tetrahydroisoquinoline, induces granulocytic differentiation of the human leukemic HL-60 cells via G0/G1 phase arrest

Tetrahydroisoquinolines are known to have various biological effects, including antitumor activity. This study investigated the effect of 1-chloromethyl-6, 7-dimethoxy-3, 4-dihydro-1H-isoquinoline-2-sulfonic acid amide (CDST), a newly synthesized anticancer agent, on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells were determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide staining, western blot analysis and immunoprecipitation, respectively. CDST induced the differentiation of HL-60, as shown by increased expression of differentiation surface antigen CD11b (but no significant change in CD14 expression) and increased NBT-reducing functional activity. DNA flow cytometry analysis indicated that CDST markedly induced a G0/G1 phase arrest of HL-60 cells. Subsequently, we examined the expre-ssion of G0/G1 phase cell cycle-related proteins, including cyclin-dependent kinases (CDKs), cyclins and cyclin dependent kinase inhibitors (CKIs), during the differentiation of HL-60. The levels of CDK2, CDK6, cyclin E and cyclin A were decreased, whereas steady-state levels of CDK4 and cyclin D1 were unaffected. The expression of the p27Kip1 was markedly increased by CDST, but not p21WAF1/Cip1. Moreover, CDST markedly enhanced the binding of p27Kip1 with CDK2 and CDK6, resulting in the reduced activity of both kinases. Taken together, these results demonstrate that CDST is capable of inducing cellular differentiation and growth inhibition through p27Kip1 protein-related G0/G1 phase arrest in HL-60 cells.

电离辐射诱导EL-4淋巴瘤细胞G_1期阻滞及相关蛋白的表达

探讨X射线诱导EL 1细胞G1期阻滞及相关蛋白的表达。采用PI荧光标记 ,流式细胞术检测细胞周期的变化。用单克隆抗体免疫荧光标记 ,流式细胞术检测蛋白表达的变化。结果表明 ,2 0Gy和 4 0Gy照射后 12 72h ,G1期EL 4细胞百分数显著高于假照射组 ( p <0 0 5- p <0 0 0 1)。 4 0Gy照射后EL 4细胞 p53蛋白表达从照射后 2h开始明显增高 ,持续至照射后2 4h ( p <0 0 5- p <0 0 0 1) ;p2 1蛋白表达在照射后 2h开始明显增高 ,持续至照射后 4 8h ( p <0 0 5- p <0 0 0 1) ;GADD4 5蛋白表达在照射后 2h开始明显增高 ,持续至照射后 4 8h ( p <0 0 5- p <0 0 0 1) ;MDM 2蛋白表达在照射后 4h开始明显增高 ,持续至照射后 2 4h ( p <0 0 5- p <0 0 0 1)。结果提示 ,中等剂量X射线照射可诱导EL 4细胞G1期阻滞。p53、p2 1和GADD4 5蛋白表达在电离辐射诱导EL

β_2受体阻滞剂诱导胰腺癌细胞G1/S期阻滞的实验研究

目的研究β_2受体阻滞剂ICI118,551诱导胰腺癌细胞G1/S期阻滞及其相关机制。方法应用β_2受体阻滞剂ICI118,551和β_1受体阻滞剂美托洛尔干预胰腺癌细胞,通过流式细胞仪检测细胞周期、Western blot技术检测β_2受体阻滞剂对细胞周期调节蛋白Cyclin D1和Cyclin E表达的影响,EMSA技术检测核转录因子NF-κB的活性,构建裸鼠肾包膜下移植瘤模型检测肿瘤增殖情况。结果 ICI118,551可显著诱导胰腺癌细胞G1/S期阻滞,并显著优于美托洛尔组(P<0.05);ICI118,551干预组抑制Cyclin D1和Cyclin E的表达,并可抑制NF-κB的活性;裸鼠肾包膜下移植瘤实验显示ICI118,551可显著抑制胰腺癌细胞的增殖。结论β_2受体阻滞剂ICI118,551可有效诱导胰腺癌细胞G1/S期阻滞,抑制胰腺癌细胞的增殖。

p16负向调控通路与辐射诱导的G_1期阻滞

辐射诱导细胞发生G1期阻滞,其分子调控机制尚不十分清楚。近期文献报道,独立于p53基因之外的p16-Cyclins-CDKs(细胞周期素依赖性激酶)细胞周期负向调控通路在紫外线和电离辐射照后发生改变,提示此通路可能在辐射诱导的G1期阻滞中发挥至关重要的作用。

p^(21)/waf1调节血管紧张素Ⅱ的抗增生作用

为了研究血管紧张素 (Ang )的抗内皮细胞增生作用及其分子生物学调节机制 ,将健康胎儿脐静脉内皮细胞培养至第 3代 ,用 Ang 培养并在不同时间计数细胞密度。用 TUNEL 或 EL ISA方法证明 Ang 或 CGP42 112 A诱导内皮细胞凋亡。用 RT- PCR和 Western Blot检测 p2 1 / waf1m RNA和 P2 1 蛋白的表达并测定条带的光密度。结果表明 ,在 Ang 培养后不同时间 ,细胞密度比对照减少 30 %左右 (P<0 .0 1)。Ang 作用后可以诱导典型的凋亡 ,阳性率极显著高于阴性对照组并具有剂量依赖性。Ang 组或 CGP42 112 A组的 p2 1 / waf1m RNA表达分别是对照组的 (4 73.6 9± 39.97) %和 (391.5 8± 48.2 4) %(P<0 .0 1)。Ang 组的 P2 1 蛋白表达比对照组极显著地增加并具有时间依赖性。认为 Ang 具有抗内皮细胞增生作用 ,其细胞内机制是同时诱导凋亡和 p2 1 / waf1m RNA与 P2 1 蛋白的高表达 ,使细胞发生 G1 期阻滞 ,增殖受抑。

ICI118,551诱导胰腺癌细胞凋亡及其机制的实验研究

目的研究ICI118,551通过调控细胞信号通路抑制抗凋亡分子的表达所产生的促凋亡效应及其机制.方法应用β2受体阻滞剂ICI118,551和β1受体阻滞剂美托洛尔干预胰腺癌细胞,通过电镜检测细胞凋亡、Hoechst 33324荧光染色检测细胞凋亡、流式细胞仪检测细胞凋亡、Western blot等技术检测β2受体阻滞剂对ERK和Akt磷酸化改变,调节细胞凋亡和细胞周期下游相关分子caspase-3、caspase-9、Bcl-2及Bax的表达.结果 ICI118,551可显著诱导胰腺癌细胞凋亡,细胞凋亡率显著大于美托洛尔组(P<0.05);ICI118,551干预组抑制Akt和ERK的磷酸化,并激活Bax、caspase-3和caspase-9活性片段的表达,同时抑制Bcl-2的表达.结论β2受体阻滞剂可以阻断相关细胞通路而进一步抑制下游相关促侵袭和抗凋亡分子的表达,并产生促凋亡效应.

MicroRNA-10a通过靶向作用E2F3抑制肝癌细胞的增殖

目的：探讨微小RNA-10a（microRNA-10a,miR-10a）对肝癌细胞增殖的影响及其作用机制。方法：收集广西医科大学附属肿瘤医院肿瘤科2001年10月至2005年7月144例肝癌患者手术切除的肝癌组织和癌旁组织（距癌灶组织边缘2~5 cm）标本,Real-time PCR法分析144例肝癌组织及癌旁组织中miR-10a的表达量。在肝癌细胞（QGY-7701、Huh7、PCL/PRF/5）中转染miR-10a模拟物,Real-time PCR法检测转染后细胞miR-10a的表达水平;CCK-8法检测过表达miR-10a的肝癌细胞的增殖水平,流式细胞术检测过表达miR-10a的肝癌细胞的凋亡和细胞周期;生物信息学预测并以Western blotting检测过表达miR-10a的肝癌细胞中转录因子E2F3的表达量。结果：与癌旁组织相比,肝癌组织中的miR-10a显著低表达[（-9.89±1.68）vs（-7.84±1.97）,P=0.000]。转染miR-10a模拟物后肝癌细胞系中miR-10a的表达量是转染对照小RNA组或空白组细胞的16倍左右。过表达miR-10a可显著抑制7种肝癌细胞（QGY-7701、QGY-7703、Huh7、PCL/PRF/5、HepG2、BeL-7402、SMMC-7721）的增殖（均P〈0.05）,并引起肝癌细胞细胞周期G1/S期阻滞,但并不能诱导肝癌细胞发生凋亡。生物信息学预测显示E2F3是miR-10a可能的靶分子,Western blotting检测显示过表达miR-10a可明显抑制肝癌细胞中E2F3的表达[（0.50±0.12）vs（0.79±0.21）,P〈0.05]。结论：人肝癌组织中低表达miR-10a,转染miR-10a模拟物后多种肝癌细胞的增殖均受到明显抑制,其机制可能与miR-10a靶向作用转录因子E2F3并阻滞肝癌细胞细胞周期于G1/S期有关。

Epigenetic Enabled Normal Human Cells, Lead to <i>First Cell</i>’s Unique Division System, Driving Tumorigenesis Evolution

Normal cells must become cancer-enabling before anything else occurs, according to latest literature. The goal in this mini-review is to demonstrate special tetraploidy in the enabling process. This we have shown from genomic damage, DDR (DNA Damage Response) activity with skip of mitosis leading to diploid G2 cells at the G1 border in need of chromatin repair for continued cell cycling to the special tetraploid division system. In several studies specific methylation transferase genes were activated in normal human cells in tissue fields, containing different cell growth stages of the cancerous process. Histology studies, in addition to molecular chemistry for identification of oncogenic mutational change, were a welcome change (see below). In a study on melanoma origin, DDR also showed arrested diploid cells regaining cycling from methylation transferase activity with causation of 2n melanocytes transforming to 4n melanoblasts, giving rise to epigenetic tumorigenesis enabled First Cells. Such First Cells were from Barrett’s esophagus shown to have inherited the unique division system from 4n diplochromosomal cells, first described in mouse ascites cancer cells (below). We discovered that the large nucleus prior to chromosomal division turned 90° relative to the cytoskeleton axis, and divided genome reductive to diploid, First Cells, in a perpendicular orientation to the surrounding normal cells they had originated from. This unique division system was herein shown to occur at metastasis stage, implying activity throughout the cancerous evolution. Another study showed 4-chromatid tetraploidy in development to B-cell lymphoma, and that such cancer cells also proliferated with participation of this unusual division system. Such participation has long been known from Bloom’s inherited syndrome with repair chiasmas between the four chromatids, also an in vitro observation by us. Our cytogenetic approach also revealed that they believed mitotic division in cancer cells is wrong because such cell divisions were found to be from an adaptation between amitosis and mitosis, called amitotic-mitosis. Amitosis means division without centrosomes, which has long been known from oral cancer cells, in that MOTCs (microtubule organizing center) were lacking centrioles. This observation calls for re-introduction of karyotype and cell division studies in cancer cell proliferation. It has high probability of contributing novel approaches to cancer control from screening of drugs against the amitotic-mitotic division apparatus.

Nanosize aminated fullerene for autophagic flux activation and G0/G1 phase arrest in cancer cells via post-transcriptional regulation

Functional fullerene derivatives exhibit special inhibitory effects on tumor progress and metastasis via diverse tumor microenvironment regulations,while the elusive molecular mechanisms hinder their clinical transformation.Herein,it is initially revealed that nanosize aminated fullerene(C_(70)-EDA)can activate autophagic flux,induce G0/G1 cell cycle arrest to abrogate cancer cell proliferation,and significantly inhibit tumor growth in vivo.Mechanismly,C_(70)-EDA promotes the expression of cathepsin D involved in autophagic activation via post-transcriptional regulation,attributing to the interaction with a panel of RNA binding proteins.The accumulation of cathepsin D induces the autophagic degradation of cyclin D1,which arouses G0/G1 phase arrest.This work unveils the fantastic anti-tumor activity of aminated fullerene,elucidates the molecular mechanism,and provides a new strategy for the antineoplastic drug development on functional fullerenes.

HIV-1 Vpr protein activates the NF-κB pathway to promote G2/M cell cycle arrest

Viral protein R(Vpr) plays an important role in the replication and pathogenesis of Human immunodeficiency virus type 1(HIV-1). Some of the various functions attributed to Vpr, including the induction of G2/M cell cycle arrest, activating the NF-κB pathway, and promoting viral reverse transcription, might be interrelated. To test this hypothesis, a panel of Vpr mutants were investigated for their ability to induce G2/M arrest and to activate the NF-κB pathway. The results showed that the Vpr mutants that failed to activate NF-κB also lost the activity to induce G2/M arrest, which suggests that inducing G2/M arrest via Vpr depends at least partially on the activation of NF-κB. This latter possibility is supported by data showing that knocking down the key factors in the NF-κB pathway – p65, Rel B, IKKα, or IKKβ– partially rescued the G2/M arrest induced by Vpr.Our results suggest that the NF-κB pathway is probably involved in Vpr-induced G2/M cell cycle arrest.

Ethanol Extract of Ilex Hainanensis Merr. Exhibits Anti-Melanoma Activity by Induction of G1/S Cell-Cycle Arrest and Apoptosis

Objective： To evaluate anti-melanoma effect of ethanol extract of Ilex hainanensis Merr. （IME） and elucidate its underlying mechanism. Methods： Thirty-six tumor-bearing mice were randomized into 6 groups （n=6） as follows： model group, IME 25, 50, 100, and 200 mg/kg groups and dacarbazine （DTIC） 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25, 50, 100 or 200 mg/kg per day, respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-（4,5-dime-thylthylthiazol-2-yl）-2, 5-diphenyl-tetrazolium bromide （MTT） assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 （NF-κB-p65）, Bcl-2, B-cell lymphoma-extra large （Bcl-xL） and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3, -8, and -9 activities were detected using the colorimetric method. In addition, a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore, a survival experiment of tumor-bearing mice was also performed to evaluate the possible toxicity of IME. Results： IME significantly inhibited the proliferation of B16-F10 cells （P〈0.01）. Flow cytometric analysis showed that IME induced G1/S cell cycle arrest and apoptosis （both P〈0.01）. IME inhibited activation of NF-κB, decreased the gene and protein expressions of Bcl-2, Bcl-xL, and increased the gene and protein expressions of Bax （all P〈0.01）. In addition, IME induced the activation of Caspases-3, -8, and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume （P〈0.01）, and the inhibitory rate came up to 68.62%. IME also induced large areas of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor volume. Survival experiment showed that treatment with IME for 14 days significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group were still alive until the 50th day. Notably, IME showed no apparent side-effects during the treatment period. Conclusion： IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.

低剂量X射线照射诱导G_1期阻滞的适应性反应

目的观察低剂量Ｘ射线照射能否诱导Ｇ１期细胞阻滞。方法采用碘化丙啶（ＰＩ）荧光探针标记细胞，流式细胞术（ＦＣＭ）检测并分析细胞周期。结果证实１．５ＧｙＸ射线全身照射后１２小时，小鼠胸腺细胞发生明显Ｇ１期阻滞。而０．０７５Ｇｙ低剂量预照射可明显减轻其后１．５Ｇｙ攻击剂量所致Ｇ１期阻滞。离体照射ＥＬ－４淋巴瘤细胞也得到类似结果。结论０．０７５ＧｙＸ射线照射能诱导胸腺淋巴细胞及ＥＬ－４细胞Ｇ１期阻滞的适应性反应。

不同剂量X射线全身照射对小鼠骨髓细胞周期进程的影响

本文采用流式细胞术研究了不同剂量 X射线全身照射后小鼠骨髓细胞周期进程的变化。结果表明 ,0 .0 75 Gy X射线全身照射后 2～ 72 h骨髓细胞周期各时相细胞百分数未发生明显变化 ;2 .0 Gy全身照射后 4 h骨髓细胞便开始出现明显的 G2 阻滞 ,12 h同时出现 G1、G2 阻滞 ,而后很快恢复到假照水平。不同剂量 (0 .0 5 Gy～ 6 .0 Gy)全身照射后 12 h量效结果表明 ,低剂量范围内 (0 .0 5～ 0 .2 Gy)骨髓细胞周期各时相细胞百分数未发生明显变化 ;较大剂量范围内 (0 .5 Gy～ 6 .0 Gy)照射后出现明显的G1、G2 阻滞 ,S期细胞百分数减少。提示低剂量全身照射后骨髓细胞周期进程未检测出变化 ;而较大剂量全身照射后 ,骨髓细胞出现 DNA合成抑制 ,G1和 G2

p21在电离辐射诱导EL-4细胞G_1期阻滞中的作用

目的 探讨 p2 1在电离辐射诱导EL 4细胞G1期阻滞中的作用。方法 采用North ernblot检测 p2 1WAF1mRNA水平的变化 ;采用流式细胞术检测 p2 1蛋白表达及细胞周期的变化。结果 4 0GyX射线照射后 12h、2 4h、48hG1期EL 4细胞百分数明显高于假照射组 ;p2 1WAF1mRNA水平从照射后 1h开始升高 ,4h达峰值 ,持续至照后 12h ;p2 1蛋白表达在照射后 2～ 48h明显增高。结论 4 0GyX射线照射可诱导EL 4细胞G1期阻滞 ,p2 1在电离辐射诱导EL 4细胞G1期阻滞中起重要作用。

昆明山海棠碱对Jurkat淋巴瘤细胞株的细胞周期和凋亡时相的影响

目的 探讨昆明山海棠 (THH)碱对JurkatT淋巴瘤细胞的细胞毒性、细胞周期和凋亡时相特异性的影响 ,以了解THH碱诱导细胞凋亡的机制。方法 台盼蓝染色法检测细胞生长和细胞活力 ;DNA染色法、TUNEL标记结合流式细胞术检测细胞周期和凋亡时相特异性。结果 THH碱能有效抑制Jurkat细胞增殖、细胞活力下降 ,细胞在增殖周期中被阻滞于G1 期。THH碱首先能诱导S、G2 M期细胞凋亡 ,同时能诱导G1 期细胞凋亡。结论 提示THH碱能抑制Jurkat细胞的DNA合成 ,抑制细胞增增殖 ,并可显著诱导各期相细胞发生凋亡。