c-Met对三阴性乳腺癌细胞增殖及阿霉素耐药性的影响

目的:研究c-Met对三阴性乳腺癌细胞株MDA-MB-231活力及对阿霉素耐药性的影响。方法:构建阿霉素耐药的MDA-MB-231/ADR细胞系,实时荧光定量PCR及Western blotting技术检测不同细胞系中c-Met mRNA及蛋白的表达。脂质体转染c-Met-siRNA及表达质粒或AKT-siRNA,Western blotting检测转染效率;四甲基偶氮唑法(MTT法)检测细胞的活力及对阿霉素的敏感性。结果:对阿霉素耐药的MDA-MB-231/ADR细胞中cMet的mRNA及蛋白表达均显著高于对照的MDA-MB-231细胞,转染高表达c-Met的质粒可增加MDA-MB-231细胞的活力并降低其对阿霉素的敏感性,而利用siRNA抑制耐药细胞株中c-Met的表达后,可以逆转MDA-MB-231/ADR细胞对阿霉素的耐药。此外,c-Met可以磷酸化激活细胞中的AKT,并通过该信号分子增加MDA-MB-231细胞活力并诱导耐药。结论:c-Met可作为一个重要的靶点应用于三阴性乳腺癌的治疗。     

表阿霉素联合索拉非尼增强乳腺癌MCF-7细胞凋亡体外研究

目的探讨表阿霉素(Epirubicin)联合分子靶向药索拉非尼(Sorafenib)对乳腺癌MCF-7细胞凋亡作用。方法采用人乳腺癌(MCF-7)细胞株。实验分为4组,即对照组、表阿霉素单药组、索拉非尼单药组、索拉非尼+表阿霉素联合组。对各组细胞给予相应药物处理,72h后经流式细胞仪检测各组药物对MCF-7细胞凋亡的作用。结果索拉非尼或表阿霉素单药作用后经流式细胞仪检测,细胞凋亡率均较对照组升高(P0.05),索拉非尼组诱导的细胞凋亡率为6.34%,表阿霉素组为13.35%。与单药组比,索拉非尼+表阿霉素联合组凋亡率升高更为明显,达23.47%(P0.05)。结论索拉非尼和表阿霉素的联合应用使抗肿瘤活性显著增强。     

低频超声联合紫杉醇对人乳腺癌MCF-7细胞增殖和凋亡的影响

目的研究低频超声和紫杉醇联合应用对乳腺癌MCF-7细胞增殖和凋亡的影响以及其可能机制。方法培养乳腺癌MCF-7细胞,随机分为4组:对照组、低频超声组、紫杉醇组和低频超声+紫杉醇组。低2频超声组为超声840k Hz,0.75W/cm×3min辐照;紫杉醇组为药物浓度为10nmol/L培养24h;联合组叠加处理因素。应用CCK-8检测细胞增殖,应用流式细胞仪和凋亡试剂盒检测各组细胞凋亡,应用流式细胞仪和ROS试剂盒检测各组细胞ROS水平,应用Western Blot实验检测凋亡相关蛋白表达。结果单独应用低频超声或紫杉醇均能抑制MCF-7细胞增殖,诱导细胞凋亡,升高细胞内活性氧水平,增加凋亡相关蛋白(cleaved caspase-3、cleaved caspase-2、Bax)的表达水平,降低Bcl-2的表达水平。与单独应用组相比,低频超声和紫杉醇联合,显著增强了上述作用。结论低频超声和紫杉醇联合作用,极大增强了抑制MCF-7细胞增殖,诱发其凋亡的作用,其作用可能和线粒体凋亡途径相关。     

紫杉醇联合表阿霉素治疗转移性乳腺癌20例

紫杉醇(paclitaxel)是上世纪90年代发现的新型广谱抗肿瘤药,具有较强的抗癌活性。我院于2002年4月至2004年6月采用紫杉醇联合表阿霉素治疗转移性乳腺癌20例,近期有效率65%,副作用小,报告如下。1资料与方法1.1一般资料本组20例均为女性,年龄在26-67(平均47岁),1例为新近发现的乳     

阿霉素对K562细胞凋亡及FAK mRNA的影响

目的探讨阿霉素体外作用于K562细胞后,观察其对细胞增殖的影响,促进细胞凋亡情况,以及调节细胞周期和粘着斑激酶（FAK）mRNA基因,进一步探讨通过调控FAK表达,研究抗白血病的作用机制。方法应用细胞增殖实验（CCK8法）观察不同浓度阿霉素作用不同时间对K562细胞增殖的影响,应用流式细胞仪观察不同浓度阿霉素对K562细胞细胞凋亡,细胞周期的影响,应用RT-PCR和Western blot技术检测不同浓度阿霉素作用对K562细胞36h后FAK mRNA以及蛋白表达水平的变化。结果随着阿霉素浓度增加及作用时间延长,K562细胞的增殖抑制率逐渐升高,同一时间不同浓度之间比较,或者同一浓度不同时间组之间比较,差异均有统计学意义（P〈0.05）;阿霉素能引起K562细胞凋亡,且随着药物浓度增加,凋亡率也逐渐增加,差异均有统计学意义（P〈0.05）;阿霉素能引起K562细胞周期阻滞,多停留在S期;阿霉素能引起K562细胞FAK mRNA表达显著降低。阿霉素能引起K562细胞FAK蛋白表达水平的降低。结论阿霉素抑制分裂期细胞的增殖,诱导细胞凋亡增加,对细胞FAK基因和蛋白水平均显著下调,为进一步研究FAK基因表达的调控与肿瘤细胞凋亡的分子机制提供了实验基础。     

下调circ＿0007031对乳腺癌细胞增殖和凋亡的影响

目的 探讨circ＿0007031对乳腺癌细胞增殖和凋亡的影响及分子机制。方法 选取33例乳腺癌患者癌组织及癌旁组织,RT-qPCR法检测circ＿0007031和miR-142-3p表达;乳腺癌细胞T47D分为si-circ＿0007031组、si-NC组、miR-142-3p组、miR-NC组、si-circ＿0007031+anti-miR-142-3p组、si-circ＿0007031+anti-miR-NC组;MTT、克隆形成实验、流式细胞术分别检测细胞增殖抑制率、集落形成数、细胞周期和细胞凋亡;双荧光素酶报告实验检测circ＿0007031和miR-142-3p的靶向关系。结果 乳腺癌组织中circ＿0007031表达水平高于癌旁组织（2.30±0.37 vs 0.95±0.15,P<0.05）,miR-142-3p表达水平低于癌旁组织（0.41±0.08vs1.09±0.17,P<0.05）。下调circ＿0007031或上调miR-142-3p,T47D细胞增殖抑制率、凋亡率升高,集落形成数减少,G0～G1期细胞所占比例增加,S期细胞所占比例减少（P<...     

光动力疗法对人乳腺癌MCF-7细胞增殖凋亡的影响

目的 研究光动力疗法（PDT）对人乳腺癌MCF-7细胞增殖的影响和诱导凋亡的作用.方法 癌光啉（PSD-007）与细胞共同孵育2h后,以不同能量635 nm激光照射,通过噻唑蓝（MTT）比色法测定PDT后不同时间（0.5、1、3、6、12、24h）细胞的光密度（0D）值及存活率.DAPI染色观察PDT后不同时间细胞凋亡中细胞核形态学的改变.Annexin-V/PI双染法结合流式细胞术分析细胞凋亡率的变化.结果 PDT对MCF-7细胞的增殖有抑制作用,且随着PDT光照能量的提高而增强,PDT作用后细胞存活率随时间延长而逐渐降低.细胞形态学观察结果表明,MCF-7细胞呈典型的凋亡形态特征.Annexin-V/PI双染也证实PDT可以诱导细胞凋亡,且凋亡率随PDT作用后时间的延长而升高.结论 PDT能显著抑制MCF-7细胞增殖,诱导细胞凋亡,且其诱导肿瘤细胞的凋亡是一渐进性的过程,具有光照剂量和时间效应关系.     

赫赛汀诱导乳腺癌细胞凋亡及对其细胞周期的影响

目的研究免疫靶向治疗药物赫赛汀(Herceptin)对HER-2过表达的乳腺癌细胞凋亡及细胞周期的影响。方法Herceptin处理体外培养的乳腺癌SKBR3细胞系,经MTT试验筛选最佳药物处理浓度和时间的组合,应用荧光显微镜、激光共聚焦显微镜、扫描电镜、透射电镜及流式细胞仪检测乳腺癌细胞凋亡的特征、凋亡细胞百分率及细胞周期的变化。结果在Herceptin作用下,荧光显微镜、激光共聚焦显微镜、扫描电镜、透射电镜观察SKBR3细胞均出现凋亡特征。Annexin/PI染色流式仪测定,药物处理组早期凋亡百分率较对照组显著增加(P<0.01)。流式仪细胞周期分析显示,S期细胞含量下降,而G2期细胞含量上升。结论免疫靶向治疗药物Herceptin可特异性地诱导HER-2过表达的乳腺癌细胞发生凋亡,并可使其生长受阻于G2期。诱导凋亡可能是Herceptin抗肿瘤作用的重要机制之一。     

恒定磁场协同阿霉素诱导肝癌细胞凋亡的研究

目的：探讨恒定磁场联合阿霉素对诱导肝癌细胞凋亡的影响。方法：采用流式细胞仪碘化丙啶染色法和活细胞荧光染色法（Ｈｏｅｃｈｓｔ染色法），观察不同处理因素对细胞凋亡率的影响。结果：两种实验方法均显示０５ｍｇ／Ｌ的阿霉素与对照组比较没有显著差异（Ｐ＞００５），而单独用恒定磁场或１０ｍｇ／Ｌ的阿霉素与对照组比较有显著性差异（Ｐ＜００５）。应用恒定磁场后发现，０５ｍｇ／Ｌ和１０ｍｇ／Ｌ浓度的阿霉素诱导ＨｅｐＧ－２细胞凋亡的结果与对照组相比，均有显著差异（Ｐ＜００５）。结论：恒定磁场具有增强阿霉素诱导肝癌细胞凋亡的作用     

纳米纤维介导的紫杉醇/阿霉素序贯联合治疗SHg-44胶质瘤

背景：纳米纤维技术可同时担载多种药物,避开血脑屏障限制实现脑胶质瘤的序贯联合化疗。 目的：用乳液电纺法制备同时担载紫杉醇和阿霉素的聚乙二醇-聚乳酸共聚物纳米纤维并实现两种药物的序贯释放,探讨纳米纤维介导的紫杉醇和阿霉素序贯联合治疗SHg-44胶质瘤的效果及机制。 方法:实验分为4组,1640培养液对照组,1%阿霉素组,1%紫杉醇组,5%(阿霉素+紫杉醇)组。采用高效液相色谱法测定紫杉醇和阿霉素的体外释放情况。四甲基偶氮唑盐法检测纳米纤维介导的紫杉醇和阿霉素序贯治疗对SHg-44胶质瘤细胞的增殖抑制率;流式细胞仪检测法检测紫杉醇和阿霉素序贯治疗对SHg-44胶质瘤细胞的凋亡诱导作用。 结果与结论：纳米纤维介导的紫杉醇和阿霉素序贯治疗对SHg-44胶质瘤细胞具有明显的生长抑制及促凋亡作用,且作用效果好于单独药物应用。提示聚乙二醇-聚乳酸纳米纤维作为一种药物载体能提高紫杉醇和阿霉素对SHg-44胶质瘤细胞增殖抑制和诱导凋亡作用。     

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin

Background: The evolution of adriamycin (ADR) resistance in the treatment of breast cancer often leads to a poor prognosis in patients. Ubiquitin-specific peptidase 37 (USP37) has been recently identified as a modulator in regulating the stemness of breast cancer cells, but its underlying mechanism remains unclear. In this study, we investigated whether USP37 knockdown could hamper the chemical resistance of MCF-7 and MCF-7/ADR cells to adriamycin and elucidated the potential mechanism.Methods: Immunohistochemistry, western blotting, and RT-qPCR assays were performed to detect the USP37 expression in MCF-7 and MCF-7/ADR cells. The efficiency of USP37 knockdown in breast cancer cells was confirmed by western blotting and RT-qPCR assays. We also performed CCK-8 assay, flow cytometry, western blotting, and TUNEL assays to evaluate cell viability and apoptosis in breast cancer cells. In vivo study was performed to detect the tumorigenicity of MCF-7/ADR cells transfected with shScramble or shUSP37#1 under adriamycin treatment.Results: Bioinformatic analysis indicated that USP37 overexpression was positively correlated with adriamycin resistance. The expression levels of USP37 in both MCF-7 and MCF-7/ADR cells increased significantly with the exposure to adriamycin in a dose-dependent manner. It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis. Furthermore, in vivo study showed that knockdown of USP37 expression also decreased tumorigenicity of MCF-7/ADR cells in mice. TUNEL assay and observation of cell morphology magnified USP37 knockdown synergized with Adriamycin could elevate the apoptosis of MCF-7 and MCF-7/ADR cells. Western blotting assay illustrated that the combination of USP37 knockdown with adriamycin treatment significantly upregulated the expression levels of cleaved caspase 3 and Bax, whereas the expression level of Bcl-2 was inhibited.Conclusion: Knockdown of USP37 gene expression can reverse the resistance of breast cancer cells to adriamycin, and down-regulating USP37 might be a valuable strategy against ADR resistance in breast cancer therapy.     

The Effects of X-Ray Irradiation on the Proliferation and Apoptosis of MCF-7 Breast Cancer Cells

Abstract

To investigate the effects of X-ray irradiation on the proliferation and apoptosis of MCF-7 breast cancer cells; MCF-7 breast cancer cells were irradiated with X-ray. After irradiation, morphological changes and growth inhibition rate of the irradiated cells were observed under an inverted microscope. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the proliferation of the irradiated MCF-7 cells. Transmission electron microscope was used to observe the morphology and ultrastructure of the irradiated MCF-7 cells. Western blotting was used to analyze the expression level of apoptosis-related protein caspase-3. Our results showed, at 48?h after the irradiation (0?Gy and 8?Gy), cells oval in shape, cell shrinkage or swelling and partial formation of debris under inverted microscope; as well as cytoplasmic vacuolization or inspissation, increased electron density of cytoplasm, structural damage of organelles, blurred mitochondrial cristae and chromatin margination under transmission electron microscopy; the survival rate of MCF-7 cells in X-ray group was 17.3% lower than that in control group (0?Gy) (p?<?0.001); while caspase-3 expression increased evidently in X-ray group compared with control group (0?Gy) (p?<?0.05). In conclusion, X-ray irradiation can inhibit the proliferation of MCF-7 cells and induce apoptosis through increasing caspase-3 expression.     

A Study on the Inhibitory Effect of Matrine on Gastric Cancer SGC-7901 Cells

The objective of this paper was to investigate the antitumour mechanism of action of matrine by studying its inhibitory effect on gastric cancer SGC-7901 cells. SGC-7901 cells were chosen, and cell-killing capacity of matrine on gastric cancer SGC-7901 cells was determined using MTT assay and single PI staining assay. The results showed that matrine had an inhibitory effect on gastric cancer SGC-7901 cells, which was somewhat dose-dependent. The study concluded that matrine has a significant in-vitro inhibitory effect on SGC-7901 tumour cells, influences cell cycle of SGC-7901 cells, and induces their apoptosis.     

绝经前乳腺癌患者术后辅助化疗对血清性激素六项的影响

目的观察绝经前乳腺癌患者术后辅助化疗对其性激素6项的影响,为临床早期评价化疗导致卵巢损伤提供检验依据。方法应用回顾性分析及统计学方法,分析39例绝经前乳腺癌患者性激素6项化疗前和化疗后各时期的水平变化。结果化疗后各周期性激素6项与化疗前比较发现:FSH、LH在第一次化疗后就开始升高,FSH、LH在第二次化疗后结果分别为:39.9(9.19~102.1)mIU/mL,14.8(3.12~42.1)mIU/mL,与化疗前7.67(3.04~31.7)mIU/mL,4.31(1.91~22.8)mIU/mL比较差异有统计学意义,P<0.01,并随着化疗周期的增加持续升高并维持在较高水平;E2和P在第一次化疗后开始降低,E2在第二次化疗为:27.48(8.09~117.1)pg/mL与化疗前的51.1(15.38~363.56)pg/mL比较差异有统计学意义,P<0.01;P第三次化疗后为0.61(0.11~1.44)ng/mL与化疗前的1.57(0.27~23.2)ng/mL比较差异有统计学意义,P<0.01,并随着化疗周期的增加持续降低并维持在较低水平;T和PRL则在化疗前后及各化疗周期水平变化不明显,差异无统计学意义,P>0.05。结论绝经期前乳腺癌患者在化疗后,血清FSH、LH、E2、P均有显著变化,可暂将血清E2<27.48 pg/mL,FSH>39.9 mIU/mL,LH>14.8 mIU/mL,P<0.61 ng/mL作为判断化疗后卵巢损伤的启动点,有一定的临床价值。     

Apoptosis Induction of Centella Asiatica on Human Breast Cancer Cells

The present study evaluated the ability of methanolic extract of Centella asiatica (Linn) Urban (Umbelliferae) to induce apoptosis in different cancer cell lines. MCF-7 cells emerged as the most sensitive cell line for in vitro growth inhibitory activity. C. asiatica extract induced apoptosis in MCF-7 cells as indicated by nuclear condensation, increased annexin staining, loss of mitochondrial membrane potential and induction of DNA breaks identified by TUNEL reactivity. It is possible that the use of C. asiatica extract as a component in herbal medicines could be justifiable.     

Effects of Selenium Yeast on Oxidative Stress,Growth Inhibition,and Apoptosis in Human Breast Cancer Cells

Recent evidence suggests that selenium (Se) yeast may exhibit potential anti-cancer properties; whereas the precise mechanisms remain unknown. The present study was aimed at evaluating the effects of Se yeast on oxidative stress, growth inhibition, and apoptosis in human breast cancer cells. Treatments of ER-positive MCF-7 and triple-negative MDA-MB-231 cells with Se yeast (100, 750, and 1500 ng Se/mL), methylseleninic acid (MSA, 1500 ng Se/mL), or methylselenocysteine (MSC, 1500 ng Se/mL) at a time course experiment (at 24, 48, 72, and 96 h) were analyzed. Se yeast inhibited the growth of these cancer cells in a dose- and time-dependent manner. Compared with the same level of MSA, cancer cells exposure to Se yeast exhibited a lower growth-inhibitory response. The latter has also lower superoxide production and reduced antioxidant enzyme activities. Furthermore, MSA (1500 ng Se/mL)-exposed non-tumorigenic human mammary epithelial cells (HMEC) have a significant growth inhibitory effect, but not Se yeast and MSC. Compared with MSA, Se yeast resulted in a greater increase in the early apoptosis in MCF-7 cells as well as a lower proportion of early and late apoptosis in MDA-MB-231 cells. In addition, nuclear morphological changes and loss of mitochondrial membrane potential were observed. In conclusion, a dose of 100 to 1500 ng Se/mL of Se yeast can increase oxidative stress, and stimulate growth inhibitory effects and apoptosis induction in breast cancer cell lines, but does not affect non-tumorigenic cells.     

PRR11在宫颈癌中的表达意义及对宫颈癌细胞增殖凋亡的影响

目的研究富含脯氨酸蛋白11(proline-rich protein 11,PRR11)在宫颈癌组织中的表达与宫颈癌患者临床病例特征及预后的关系,并探讨PRR11对宫颈癌细胞增殖凋亡的影响及作用机制。方法免疫组化检测PRR11在60例宫颈癌组织和20例正常宫颈组织中的表达水平,并分析宫颈癌组织中PRR11的表达与临床病例特征的关系及患者预后的影响。Western-blot检测PRR11蛋白在宫颈癌细胞系HeLa和人宫颈上皮永生化细胞H8中的表达;HeLa经脂质体分别转染PRR11 siRNA(si-PRR11)和对照(si-NC)48h后,采用MTS实验检测各组细胞增殖能力,流式细胞仪检测各组细胞周期阻滞和凋亡情况,Western-blot检测各组细胞中CyclinD1、caspase-3蛋白的影响。结果免疫组化结果显示宫颈癌组织中PRR11的阳性表达率显著高于正常宫颈组织中的表达,PRR11阳性表达与宫颈癌肿瘤大小及组织学分级显著相关(P均<0.05),宫颈癌组织中PRR11阳性表达患者生存期较短。PRR11在宫颈癌细胞系HeLa中的表达均显著高于人宫颈上皮永生化细胞H8(P<0.05);转染PRR11 siRNA后,HeLa细胞增殖能力下降、细胞阻滞在G1期,凋亡细胞增多,CyclinD1蛋白表达减少,caspase-3蛋白表达增加(P均<0.05)。结论PRR11在宫颈癌组织和细胞系中均高表达,且高表达与肿瘤大小、组织学分级及不良预后相关,同时PRR11可能通过调控CyclinD1、caspase-3蛋白促进宫颈癌增殖和抑制细胞凋亡,PRR11可以作为治疗子宫颈癌的潜在分子靶点。     

Fatigue in Breast Cancer Patients on Adjuvant Treatment: Course and Prevalence

Introduction:

Fatigue is a major complain in breast cancer patients and survivors. Patterns and degree varies with schedule and type of the treatment. Different co-factors may aggravate fatigue. Multimodal approach is helpful in managing fatigue.

Aim:

To quantify prevalence, course and degree of fatigue in breast cancer patients on adjuvant treatment and effectiveness of different management approach.

Materials and Methods:

One Hundred and ten post-mastectomy breast cancer patients (Stage I to Stage III) were assessed. Patients on chemotherapy were assessed one week before, day after chemotherapy and two weeks later in every cycle. Patients on External Beam Radiation Therapy (EBRT) were assessed one week before and every week during radiation. Assessment was continued on second and fourth week of follow up. Functional Assessment of Chronic Illness Therapy - Fatigue subscale (FACIT-F) was used for assessment. Significant cofactors were also searched for.

Results:

Eighty four percent patients experienced fatigue. Fatigue was more prevalent during chemotherapy (91%) than EBRT (77%). Patients on Chemotherapy exhibit peak fatigue day after Chemotherapy and decreased level until the next cycle. Significant increase of fatigue was seen only in first cycle. Patient on EBRT had gradually increased fatigue during the course of treatment. Lower degree of fatigue was present in post treatment period. Anemia was a significant cofactor causing fatigue (P < 0.05). Blood Transfusion improved fatigue scores.

Conclusion:

Fatigue increases during chemotherapy and or EBRT. Different intervention strategies are needed to address the issue.     

植入式输液港与PICC置管应用于乳腺癌术后化疗的优势

目的 分析植入式静脉输液港（VPA）与经外周置入中心静脉导管（PICC）应用于乳腺癌术后化疗的优势。方法 选择2017年6月~2019年6月在我院化疗的乳腺癌患者120例,采用随机数字表法分为对照组和观察组,各60例。对照组采用PICC置管,观察组采用VPA置管,比较两组患者一次性置管率、导管留置时间、管路维护时间、非计划性拔管率、置管期间并发症发生率以及日常生活能力。结果 观察组一次性置管率为98.33%、非计划性拔管率为3.33%分别与对照组的96.67%、6.67%比较,差异均无统计学意义（P＞0.05）;观察组导管留置时间为（4.65±1.22）个月,长于对照组的（2.42±0.87）个月,管路维护时间为（11.12±2.16）min,短于对照组的（15.52±2.35）min（P＜0.05）;观察组置管期间并发症发生率为5.00%,低于对照组的18.33%（P＜0.05）;观察组日常生活能力评分高于对照组（P＜0.05）。结论 VPA置管优势大于PICC置管,并发症发生率低,置管时间长,具有良好的临床应用效果。