p75NTR阳性人食管鳞癌细胞的干细胞特性研究

目的探讨p75NTR阳性人食管鳞癌细胞的干细胞特性。方法取15例新鲜人食管鳞癌组织制成单细胞悬液,分别获取p75NTR阳性和p75NTR阴性细胞,进行Transwell侵袭试验、耐化疗药物试验及裸鼠成瘤试验。结果15例新鲜人食管鳞癌组织中有7例发现p75NTR表达,其阳性表达率最高为10.37%,p75NTR阳性和p75NTR阴性细胞在侵袭性、对化疗药物的耐受能力及致瘤能力上差异有统计学意义。结论 p75NTR阳性较p75NTR阴性食管鳞癌细胞具有更强的侵袭性、耐化疗能力及致瘤能力,可能富集人食管鳞癌干细胞。     

神经生长因子受体p75NTR对肝癌细胞凋亡的影响及其关键功能域

目的 了解神经生长因子(nerve growth factor,NGF)受体p75NTR在肝癌组织和肝癌细胞株HepG2中的表达,探讨p75NTR对肝癌细胞凋亡的影响及其关键功能域.方法 收集2006年9月至2008年4月于华中科技大学同济医学院附属同济医院行手术切除患者的肝癌组织标本及对应的癌旁组织标本共26对,应用...     

p38在二硫苏糖醇与顺铂诱导食管癌Eca109细胞凋亡中的作用

将人食管癌Eca109细胞分为七组,其中三组分别加二硫苏糖醇(DTT,Ds)、顺铂(Cs)及二药联合(Ds Cs)处理细胞,另三组则先用磷酸化p38特异性抑制剂SB203580孵育,再分别加Ds、Cs及Ds Cs处理细胞,未加药组作为对照(C′).采用流式细胞仪技术检测细胞凋亡率.结果与C′比较,各组均存在明显差异(P均＜0.01); SB203580孵育细胞后,与相应组别比较,Ds 、Cs 、Ds Cs凋亡率均明显下降(P均＜0.01).证实p38 MAPK在Ds 和Cs诱导食管癌Eca109细胞凋亡中被显著激活,p38 MAPK的激活可能是多种上游凋亡信号传导必经的共同通路.     

甘草甜素对人食管癌细胞ECA109的影响及机制

目的探讨甘草甜素对人食管癌细胞ECA109增殖、周期和凋亡的影响及可能的作用机制。方法采用甘草甜素处理的人食管癌细胞株ECA109细胞设定为实验组,甘草甜素未处理的细胞设定为对照组。采用CCK8法检测甘草甜素对细胞增殖的影响,流式细胞术检测细胞的周期与凋亡情况,并用RT-PCR与Western印迹检测细胞中bax,bcl-2及p53 mRNA和蛋白表达水平。结果随着甘草甜素处理时间的延长和处理浓度的增加,甘草甜素对食管癌细胞增殖的抑制作用逐渐增加,具有时间剂量依赖性。流式细胞仪检测提示甘草甜素能够诱导细胞的凋亡,实验组的细胞凋亡比例显著高于对照组(P<0.05)。同时甘草甜素能够将细胞阻滞在G1期,与对照组相比差异有统计学意义(P<0.05)。甘草甜素处理后,细胞中bax,p53 mRNA与蛋白的表达水平明显增加(P<0.05),而bcl-2 mRNA与蛋白的表达明显降低(P<0.05),并且bax/bcl-2的比值增加(P<0.05)。结论甘草甜素能够延长细胞G1期时间而抑制细胞增殖,促进细胞的凋亡,其机制可能与调控bax,bcl-2及p53多种凋亡相关基因的表达有关。     

鸦胆子油乳对肺癌A549细胞顺铂化疗的增敏作用及其机制

目的 观察鸦胆子油乳对肺癌A549细胞顺铂化疗的增敏作用并分析其机制。方法 体外培养人肺癌细胞A549,MTT法检测鸦胆子油乳、顺铂对细胞生长的抑制率,计算鸦胆子油乳、顺铂对细胞的半数抑制浓度（IC50）,观察不同浓度（2.44、9.77、78.12μg/mL）鸦胆子油乳对顺铂IC50的影响。将A549细胞分为对照组、鸦胆子油乳组、顺铂组及鸦胆子油乳+顺铂组,对照组不做处理正常培养细胞,鸦胆子油乳组、顺铂组及鸦胆子油乳+顺铂组分别给予鸦胆子油乳单药、顺铂单药、鸦胆子油乳及顺铂联合处理。采用荧光显微镜观察细胞形态及生长情况,流式细胞术检测细胞周期及细胞凋亡率,二氯荧光素二乙酸酯荧光探针染色检测细胞内ROS水平。结果 顺铂IC50随着鸦胆子油乳处理浓度的增高而下降（P均<0.05）。对照组细胞生长较好,细胞数量较多且形状为正常生长状态;顺铂组及鸦胆子油乳组细胞数量较对照组均减少,可见少量碎片;鸦胆子油乳+顺铂组细胞生长受抑制较明显,细胞数量最少,细胞形状不规则且细胞碎片增多。G0/G1期细胞比例鸦胆子油乳+顺铂组>顺铂组、鸦胆子油乳组>对照组,细胞凋亡率鸦胆子油乳+顺铂组...     

己酮可可碱对人食管癌细胞EC9706的5-Fu化疗增敏作用

目的探讨己酮可可碱对人食管癌细胞EC9706的5-Fu化疗增敏作用。方法采用MTT法测定5-Fu及己酮可可碱联合5-Fu对EC9706细胞的抑制作用。结果不同浓度的己酮可可碱联合5-Fu作用于EC9706 12、24、48、72 h,同一时间各组抑制率差异有统计学意义(P均<0.01),同一5-Fu浓度,随着己酮可可碱药物浓度的增加,5-Fu对己酮可可碱细胞的抑制作用也增强(P均<0.01)。25μg/mL 5-Fu联合己酮可可碱(0.5 mg/mL、1.0mg/mL)与50μg/mL 5-Fu对EC9706细胞抑制作用,在24、48、72 h无统计学差异(P均>0.05)。结论己酮可可碱可以增加EC9706细胞对5-Fu的敏感性,减少5-Fu的剂量。     

莪术醇联合顺铂对人食管癌109细胞凋亡以及细胞核因子-κB 表达的影响

目的：研究中药莪术醇联合顺铂对食管癌109细胞系的增殖凋亡、核因子（NF）-κB表达的影响,探讨莪术醇抗肿瘤的分子机制。方法将不同浓度莪术醇、顺铂、莪术醇和顺铂联合作用于食管癌109细胞,用噻唑蓝比色法（MTT 法）检测细胞增殖,流式细胞仪检测细胞凋亡, Western blot 法检测作用48小时后细胞 NF-κB 蛋白的表达情况。结果不同浓度莪术醇、顺铂均对食管癌细胞均有抑制增殖、促进凋亡作用,抑制率、凋亡率呈明显浓度依耐性;联合用药后抑制率、凋亡率显著提高,差异有统计学意义（P ＜0．05）;4个浓度的莪术醇与顺铂（2．5 mg／L）作用食管癌48小时后 NF-κB 的表达量随浓度增加而下降,与对照组比较差异有统计学意义（P ＜0．05）。结论中药莪术醇对人食管癌109细胞株有明显抑制增殖,诱导凋亡的作用,其机制可能与下调NF-κB 蛋白的表达有关。     

肿瘤坏死因子受体p55/p75在重症急性胰腺炎发病机制中的作用

目的探讨肿瘤坏死因子受体p55/p75(TNFR p55/TNFR p75)在重症急性胰腺炎(SAP)发病机制中的作用。方法36只雄性SD大鼠均分为对照组与SAP组。SAP组采用5%牛黄胆酸钠1ml/kg胰胆管逆行穿刺注射建立模型,对照组仅给予剖腹假手术。两组大鼠分别在造模后3、6和12h处死,收集外周血与胰腺标本。ELISA法检测血清TNFα水平,RT PCR法检测外周血单个核细胞(PBMC)与胰腺组织中TNFR p55/TNFR p75mRNA表达,采用血清淀粉酶与病理组织学评分作为SAP严重程度的指标。结果SAP组不同时间点血清淀粉酶、TNFα水平及胰腺组织炎症评分均显著高于对照组(P<0.01)。在PBMC中TNFR p55/TNFR p75mRNA的表达在各时间点均较对照组显著上调(P值均<0.01),且在6h达峰值,分别为1.32±0.07和0.95±0.04;而对照组在6h点为0.84±0.01和0.68±0.04。胰腺组织中TNFR p55/TNFR p75mRNA的表达在各时间点也均高于对照组(P值均<0.05)。结论TNFα是SAP病程中重要的细胞因子并可能通过结合胰腺组织中TNFR p55/TNFR p75参与胰腺组织损伤;同时,TNFα又可能通过与PBMC中TNFR p55/TNFR p75相互作用导致外周血中白细胞活化,从而加重胰腺炎的严重程度。     

p75NTR对兔心肌梗死模型跨室壁瞬时外向钾电流异质性的作用

目的:通过干预神经营养因子p75受体(p75NTR)探讨心肌梗死(MI)后神经过度增生对心肌细胞Ito,f异质性的影响。方法:选日本大耳兔40只随机分为陈旧性心梗(HMI)组、p75 NTR激活组、p75 NTR抑制组和假手术组,每组10只(n=10)。采用酶解法制备3层心室肌单细胞,利用全细胞膜片钳技术记录电流。结果:在以+50mV的去极化刺激时,HMI组的Ito,f峰电流密度有所下降,在以p75NTR受体激活后,3层心肌Ito,f峰电流密度的下降更为明显,与假手术组比差异显著(P0.05或P0.01),其中以中层心肌Ito,f峰电流密度的下降程度最大;而应用p75NTR抑制剂后,下降的程度降低,与假手术组比无明显差异。与对照组相比,中层心肌细胞的Ito,f电压依赖性失活曲线在p75NTR激活组及HMI组均向负移,p75NTR抑制组得以恢复。Ito,f通道关闭态的τ值在4组的3层心肌细胞间存在明显差异,即p75NTR激活组及HMI组失活较快,尤以p75NTR激活组为甚,p75NTR抑制组的关闭态失活与对照组接近。结论:p75NTR激活后,3层心肌Ito,f峰电流密度下降明显,尤其以中层细胞为甚,此可能是导致跨室壁复极离散度显著增加,最终引起心律失常发生的原因之一。     

miR-485-5p对结肠癌细胞顺铂耐药的影响

目的:探讨miR-485-5p通过PI3K/Akt-PAK1信号通路对结肠癌细胞顺铂耐药的影响。方法:构建LoVo/DDP细胞株,将建LoVo/DDP细胞株分为NC组(未做转染处理)、miR-485-5p mimics组(转染miR-485-5p mimics)、miR-485-5p inhibitors组(转染miR...     

Abnormal cell proliferation in the p75NTR‐positive basal cell compartment of the esophageal epithelium during squamous carcinogenesis

The low affinity neurotrophin receptor p75NTR is known to be expressed in the mitotically quiescent basal layer (BL) of the normal esophageal epithelium. The aim of the present study was to detect oncogenic changes in the p75NTR‐positive BL during esophageal squamous carcinogenesis. The normal epithelium (NE), low‐grade intraepithelial neoplasia (LGN), high‐grade intraepithelial neoplasia (HGN), and esophageal squamous carcinoma (SCC), in which invasion was limited to the muscularis mucosa, were obtained from surgically removed esophagi. The expression of p75NTR, the proliferation marker ki67, hTERT, p53, and p63 was examined immunohistochemically. The expression of p75NTR was detected in these tissues with average staining indexes (number of stained cells/100 nucleated cells; SI) of 1.00, 0.99, 0.81, and 0.73, respectively. The expression of ki67 in the BL significantly increased with the progression from LGN to HGN. The expression of hTERT and p53 significantly increased with the progression from NE to LGN, and then increased in a stepwise manner in HGN and SCC, with SI (hTERT/p53) of 0.10/0.11, 0.32/0.45, 0.50/0.72, and 0.65/0.61, respectively. The expression of p63 showed no significant difference among NE, LGN, HGN, and SCC, with SI of 0.82, 0.77, 0.85, and 0.87, respectively. A correlation was observed between the expression of ki67 and p53 (P = 0.005), while a negative correlation was found between p75NTR and hTERT (P = 0.01). Our results demonstrated that phenotypic changes from quiescent to active proliferation in the p75NTR‐positive BL occurred during the progression from LGN to HGN. The altered expression of hTERT and p53 in the BL was detected in LGN, which suggested that additional oncogenic events that disrupt mitotic regulation in the p75NTR‐positive quiescent BL may play a crucial role in malignant transformation. Further investigations using the isolation and tracing of p75NTR‐positive cells in precancerous epithelia may provide us with a better understanding of squamous carcinogenesis.     

Activated hepatic stellate cells overexpress p75NTR after partial hepatectomy and undergo apoptosis on nerve growth factor stimulation.

BACKGROUND: Expression of neurotrophins (NTs) and their receptors is increased during hepatic regeneration, but their role is not well understood. METHODS: NTs and their receptors were investigated by RT-PCR and immunostaining in regenerating livers after two-thirds hepatectomy (PH) and in hepatocytes and hepatic stellate cells (HSCs) isolated from regenerating livers in mice. Induction of apoptosis after treatment with NGF and the expression of alpha-smooth muscle actin (SMA), interleukin 6 (IL-6) and hepatocyte growth factor (HGF) were also investigated in regenerating HSCs. RESULTS: Nerve growth factor (NGF) and p75 NT receptor (p75NTR) mRNA were elevated after PH, while other NTs and NT receptors showed no remarkable change. NGF was detected in regenerating hepatocytes, but not in normal hepatocytes. Regenerating HSCs expressed increased p75NTR and SMA in vivo and showed an activated phenotype and the high expression of HGF and IL-6 in vitro. Enhanced cell death was seen in HSCs, both from normal and regenerating liver, after treatment with NGF. CONCLUSIONS: Although activated HSCs may produce the factors that regulate liver regeneration, the de novo NGF production by regenerating hepatocytes may induce the death of activated HSCs via p75NTR, leading to termination of hepatic regeneration.     

Changes in p53 and Waf1p21 expression and cell proliferation in esophageal carcinogenesis

AIM: To study the correlation between changes in p53 and Waf1p21 expression and cell proliferation, determined by proliferating cell nuclear antigen (PCNA), at different stages of human esophageal carcinogenesis.METHODS: Biopsied and resected esophageal tissues from a high risk population of esophageal cancer in northern China were used in this study. All specimens were fixed in 85% alcohol and processed for routine histology. The avidin biotin peroxidase complex (ABC) method was used to detect p53, Waf1p21 and PCNA.RESULTS: Strong nuclear staining of p53, Waf1p21 and PCNA was observed in normal esophageal epithelium and epithelia with different lesion severities. As the lesions progressed to dysplasia (DYS) and to esophageal squamous cell carcinoma (SCC), the Waf1p21 immunoreactivity percentage decreased. The number of Waf1p21-positive cells slightly increased from normal to basal cell hyperplasia (BCH), but did not further increase in DYS and SCC. The total number of Waf1p21-positive cells was lower than the number of p53-positive cells in normal and BCH esophageal epithelia and much lower in DYS and SCC. Waf1p21-positive cells were located in the third and fourth cell layers in half of the samples examined, which was 2-4 cell layers higher than the cells expressing PCNA and p53 in the same histological categories of normal, BCH and DYS.CONCLUSION: Low Waf1p21 levels at the DYS stage may be related to a functional loss of p53. Other mechanisms may also be responsible for the decreased Waf1p21 expression in DYS and SCC.     

Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P<0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P<0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.     

亚砷酸诱导人食管癌细胞株EC109细胞p15INK4B基因的表达

目的：研究亚砷酸(As_2O_3)对人食管癌EC109细胞株细胞周期蛋白依赖性激酶抑制因子p15~(INK4B)(p15)基因表达的影响．方法：终浓度2μmol/L的As_2O_3加入食管癌EC109细胞系,采用甲基化特异PCR(MSP)检测食管癌EC109细胞系中p15基因甲基化,采用RT-PCR和Western blot方法检测As_2O_3处理前后p15的mRNA和蛋白质水平的表达情况．用Scion Image软件测量条带灰度值,P15蛋白与ACTB条带的灰度比进行半定量分析．结果：EC109细胞p15基因发生高甲基化,p15基因不表达．As_2O_3作用后p15基因甲基化程度明显下降,As_2O_3作用72,48,24 h组和未加药组之间差异均有统计学意义(37．11±3．62,50．92±5．47,72．07±7．53 vs 97．23±9．80,P＜0．05)．As_2O_3作用24 h后出现p15 mRNA表达,随As_2O_3作用时间延p15 mRNA表达逐渐增强,各个时间组之间比较,除了未加药组和加药24 h组之间及加药24 h组和加药48 h组之间差异无统计学意义外,其余各个时间组之间差异有统计学意义(0．72±0．07 vs 0．58±0．06 vs 0．48±0．07 vs 0．41±0．08,P＜0．05)．As_2O_3作用24 h后P15蛋白出现表达,2μmol/L作用24-72 h中P15蛋白条带灰度逐渐增强,As_2O_3作用72,48,24 h组和未加药组之间差异均有统计学意义(0．51±0．02 vs 0．21±0．01 vs 0．16±0．02 vs 0．06±0．01,P＜0．05),说明其表达随As_2O_3作用时间延长而逐渐增强．结论：As_2O_3可使食管癌EC109细胞p15基因去甲基化,使p15基因表达上调,从而抑制细胞周期进程．     

MiR-590-3p在胰腺癌干细胞中的表达

目的 应用无血清培养基分离胰腺癌干细胞,检测其miR-590-3p的表达。方法 运用无血清培养基克隆培养ASPC-1、PANC1细胞,检测其单克隆形成、分化及细胞周期、半数抑制浓度(IC50)和表面标记物CD24+、CD44+表达。实时定量PCR法检测细胞miR-590-3p的表达。结果 经无血清培养基培养,(0.94±0.53)％的ASPC-1细胞和(0.57±0.12)％的PANC1细胞能存活,呈克隆球样悬浮生长,并可以在体外连续传代。加入血清后细胞球又重新贴壁生长。ASPC-1细胞球G0/G1期比例和CD24+、C44+、CD24+ CD44+的细胞比例及IC50分别为(75.3±5.4)％、0.96％～2.01％、27.52％～34.47％、0.35％ ～0.44％和(224.37±5.71) μg/ml,均显著高于亲本细胞的(43.7±3.8)％、0.38％～0.42％、17.65％ ～ 18.25％、0.05％～ 0.08％、(11.43±2.10) μg/ml(P值均＜0.05)。PANC1细胞球G0/G1期比例和CD24+、CD44+、CD24 +CD44+的细胞比例及IC50分别为(80.1±4.7)％、5.31％ ～9.84％、72.05％ ～93.06％、4.91％ ～5.21％、(296.58±4.27) μg/ml,均显著高于亲本细胞的(46.1±5.3)％、4.09％～4.97％、47.71％～55.66％、1.48％ ～2.63％、(26.17±3.81) μg/ml(P值均＜0.05)。ASPC-1、PANC1细胞球miR-590-3p表达分别是亲本细胞的4.67和4.52倍。结论 应用无血清培养基可以从ASPC-1、PANC1细胞系中分离出具有干细胞特性的胰腺癌细胞球,其miR-590-3p表达上调,该基因可能是胰腺癌干细胞特性维持的关键基因。     

Differential expression of retinoic acid receptors and p53 protein in normal, premalignant, and malignant esophageal tissues

Purpose: Esophageal cancer remains a significant health problem worldwide. The very low 5-year survival rates and rapid increase in the incidence of adenocarcinoma indicate the urgent need for early identification of and new approaches to the prevention and treatment of this cancer. Methods: To find biomarkers for early identification of the disease, we analyzed nuclear retinoic retinoid receptor mRNAs, p53 protein, and the proliferation marker Ki 67 in surgical specimens of normal, mildly, and severely dysplastic and malignant esophageal tissues. Results: Nuclear retinoid receptors (RAR-α, RAR-γ, and RXR-α) were expressed in most (79%–100%) normal, dysplastic, and malignant esophageal mucosae, whereas expression of RAR-β was progressively lost from normal esophagus to carcinoma (84%–54%). In contrast, expression of p53 protein and Ki 67 were dramatically increased in severely dysplastic and cancerous tissues of the esophagus (from 5% to 62%). Conclusions: Loss of RAR-β expression and accumulation of p53 and Ki 67 proteins may serve as biomarkers for esophageal cancer. Received: 17 April 2000 / Accepted: 12 July 2000     

食管癌组织芯片p53、p16和环氧合酶-2表达的研究

目的食管癌的发生发展是多步骤、多基因变化的演化过程，本研究利用高通量的组织芯片技术，对食管癌组织及癌旁组织的p53、p16和环氧合酶（COX）-2蛋白异常表达进行分析，探讨其相关性及临床意义。方法利用组织芯片技术结合免疫组化法检测86例食管癌组织、40例癌旁组织中p53、p16、COX-2蛋白的表达。结果食管癌组织中p53、COX-2的阳性表达率均显著高于癌旁组织（P〈0．05）。食管癌组织中p16阳性表达率为5．81％，癌旁组织中没有发现p16蛋白表达，差异无统计学意义。p53与p16、p53与COX-2、p16与COX-2蛋白表达均存在差异（P〈0.05）。p53或COX-2表达阳性时组织芯片病理类型为癌性的概率增加，但p16、p53和COX-2三者不存在交互作用。结论p53、COX-2对预测和早期诊断食管癌具有重要意义。     

Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells

Cancer stem cells (CSCs) with enhanced tumorigenicity and chemoresistance are believed to be responsible for treatment failure and tumor relapse in ovarian cancer patients. However, it is still unclear how CSCs survive DNA-damaging agent treatment. Here, we report an elevated expression of DNA polymerase η (Pol η) in ovarian CSCs isolated from both ovarian cancer cell lines and primary tumors, indicating that CSCs may have intrinsically enhanced translesion DNA synthesis (TLS). Down-regulation of Pol η blocked cisplatin-induced CSC enrichment both in vitro and in vivo through the enhancement of cisplatin-induced apoptosis in CSCs, indicating that Pol η-mediated TLS contributes to the survival of CSCs upon cisplatin treatment. Furthermore, our data demonstrated a depletion of miR-93 in ovarian CSCs. Enforced expression of miR-93 in ovarian CSCs reduced Pol η expression and increased their sensitivity to cisplatin. Taken together, our data suggest that ovarian CSCs have intrinsically enhanced Pol η-mediated TLS, allowing CSCs to survive cisplatin treatment, leading to tumor relapse. Targeting Pol η, probably through enhancement of miR-93 expression, might be exploited as a strategy to increase the efficacy of cisplatin treatment.Ovarian cancer is the most lethal malignancy of the female reproductive tract with a 5-y survival rate of only 27% in advanced stages (1). The American Cancer Society estimates that in 2014, about 21,980 new cases of ovarian cancer will be diagnosed and 14,270 women will die of ovarian cancer in the United States (1). The mainline treatment of ovarian cancer is cytoreductive surgery followed by platinum (Pt)-based chemotherapy (2). Chemotherapy with Pt is initially effective for most patients. However, the majority eventually becomes refractory to Pt treatment, and around 70% of patients have tumor relapses (3). Poor understanding of the underlying mechanisms of this acquired drug resistance and tumor relapse poses a critical cancer research challenge.cis-diamminedichloroplatinum(II) (cisplatin), the first member of Pt-based chemotherapeutic agents, has been widely used to treat various malignant tumors, including ovarian cancer (4). Mechanistically, cisplatin reacts with DNA bases to cross-link adjacent purines. These cross-links block DNA replication and invoke apoptosis in rapidly dividing cells (5). Thus, the preferential activation of the DNA damage responses, especially the efficient removal of these DNA lesions, or prompt rescue of the replication, will prevent replication fork collapse and promote survival of the cells upon cisplatin treatment, eventually leading to cisplatin resistance. The cisplatin-induced DNA cross-links are primarily removed by the nucleotide excision repair (NER) pathway (6) or bypassed during replication through translesion DNA synthesis (TLS) (7–10). TLS is mediated by specialized DNA polymerases (Pols), which are characterized by low fidelity and an ability to replicate across certain types of damaged sites in template DNA with the assistance of monoubiquitylated proliferating cell nuclear antigen (ub-PCNA) (11). TLS rescues cells from the collapse of the replication fork and thus is believed to contribute to the development of cisplatin resistance (8, 12–17).It has been increasingly evident that heterogeneous ovarian cancers contain a subpopulation of cancer stem cells (CSCs) with enhanced tumorigenicity and chemoresistance. These CSCs are believed to be responsible for treatment failure and tumor relapse. Ovarian CSCs have been successfully isolated, based on the expression of distinctive cell surface markers CD44 and CD117 (18, 19), their ability to efflux the Hoechst 33342 fluorescent dye (Side population, SP) (20), the activity of ALDH (21), and their ability to grow as floating spheres in serum-free medium (19). The CD44⁺CD117⁺ cells, SP cells, ALDH⁺ cells, and spheroid cells isolated from both ovarian cancer cell lines and primary human ovarian tumors fulfill all currently accepted criteria for the existence of a subpopulation of tumor-initiating cells (19, 22, 23). Most importantly, these CSCs also demonstrate increased cisplatin resistance. However, it is still unclear how CSCs survive cisplatin treatment. In this study, we demonstrated that the expression level of TLS Pol η is higher in ovarian CSCs isolated from both cancer cell lines and primary tumors than the bulk cancer cells. Down-regulation of Pol η expression blocked cisplatin-induced enrichment of the CSC population, through facilitating the killing of CSCs by cisplatin. Mechanistic investigation demonstrated that decreased expression of miR-93 in ovarian CSCs contributes, at least partially, to the enhanced expression of Pol η. Taken together, our study suggests that Pol η-mediated TLS could be a target to facilitate the eradication of ovarian CSCs by cisplatin.