Spontaneous xenogeneic GvHD in Wilms'tumor Patient-Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg-PrkdcIl2rg(NOG)mice are among the ideal animal recipients for generation of human cancer models.Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes(TILs)can induce xenogeneic graft-versus-host disease(xGvHD)following engraftment and expansion of the TILs inside the animal body.Wilms’tumor(WT)has not been recognized as a lymphocyte-predominant tumor.However,3 consecutive generations of NOG mice bearing WT patient-derived xenografts(PDX)xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention.In the initial generation,dermatitis,auto-amputation of digits,weight loss,lymphadenopathy,hepatitis,and interstitial pneumonitis were observed.Despite antibiotic treatment,no response was noticed,and thus the animals were prematurely euthanized(day 47 posttransplantation).Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti-human CD3 and CD8 antibodies in the xenografts and primary tumor,whereas no microbial infection or lymphoproliferative disorder was found.Mice of the next generation that lived longer(91 days)developed sclerotic skin changes and more severe pneumonitis.Cutaneous symptoms were milder in the last generation.The xenografts of the last 2 generations also contained TILs,and lacked lymphoproliferative transformation.The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD.While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts,this report for the first time documented serial xGvHD in consecutive passages of WT PDX-bearing models and discussed potential solutions to prevent such an undesired complication.

Establishment of various biliary tract carcinoma cell lines and xenograft models for appropriate preclinical studies

We recently reported several driver genes of biliary tract carcinoma(BTC) that are known to play important roles in oncogenesis and disease progression. Although the need for developing novel therapeutic strategies is increasing, there are very few BTC cell lines and xenograft models currently available for conducting preclinical studies. Using a total of 88 surgical BTC specimens and 536 immunodeficient mice, 28 xenograft models and 13 new BTC cell lines, including subtypes, were established. Some of our cell lines were found to be resistant to gemcitabine, which is currently the first choice of treatment, thereby allowing highly practical preclinical studies to be conducted. Using the aforementioned cell lines and xenograft models and a clinical pathological database of patients undergoing BTC resection, we can establish a preclinical study system and appropriate parameters for drug efficacy studies to explore new biomarkers for practical applications in the future studies.

Patient-derived xenograft model in colorectal cancer basic and translational research

Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and helpful for improving CRC treat-ment.With huge efforts made in past decades,the systematic treatment regimens have been applied to improve the prognosis of CRC patients.However,the sensitivity of CRC to chemotherapy and targeted therapy is different from person to person,which is an important cause of treatment failure.The emergence of patient-derived xenograft(PDX)models shows great potential to alleviate the straits.PDX models possess similar genetic and pathological characteristics as the features of primary tu-mors.Moreover,PDX has the ability to mimic the tumor microenvironment of the original tumor.Thus,the PDX model is an important tool to screen precise drugs for individualized treatment,seek predictive biomarkers for prognosis supervision,and evaluate the unknown mechanism in basic research.This paper reviews the recent advances in constructed methods and applications of the CRC PDX model,aiming to provide new knowledge for CRC basic research and therapeutics.

Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.CONCLUSION In our experience, the faster development andgreatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer.

Combination Therapy of Capecitabine with Cyclophosphamide as a Second-Line Treatment after Failure of Paclitaxel plus Bevacizumab Treatment in a Human Triple Negative Breast Cancer Xenograft Model

We examined the antitumor efficacy of the capecitabine (CAPE) plus cyclophosphamide (CPA) combination as a 2nd-line therapy after paclitaxel (PTX) plus bevacizumab (BEV) treatment in a xenograft model of human triple negative breast cancer (TNBC) cell line, MX-1. After tumor growth was confirmed, PTX (20 mg/kg;i.v.) + BEV (5 mg/kg;i.p.) treatment was started (Day 1). Each agent was administered once a week for 5 weeks and tumor regression was observed for at least the first 3 weeks. For 2nd-line treatment, we selected mice in which the tumor volume had increased from day 29 to day 36 and was within 130 - 250 mm3 on day 36. After randomization of mice selected on day 36, CPA (10 mg/kg;p.o.) and CAPE (539 mg/kg;p.o.) were administered daily for 14 days (days 36 - 49), followed by cessation of the drugs for 1 week. The tumor growth on day 57 was significantly suppressed in the CPA, CAPE and CAPE + CPA groups as compared with the control group (p < 0.05). Furthermore, the antitumor activity on day 57 of CAPE + CPA was significantly stronger than that of CPA or CAPE alone (p < 0.05). The thymidine phosphorylase (TP) level in tumor tissue was evaluated by immunohistochemistry on day 50, and was significantly higher in the CPA group than those in the control group (p < 0.05). Upregulation of TP in tumor tissues by CPA treatment would increase the 5-FU level in tumor tissues treated with CAPE. This would explain the possible mechanism that made CAPE + CPA superior to CAPE alone in the 2nd-line treatment. Our preclinical results suggest that the CAPE + CPA combination therapy may be effective as 2nd-line therapy after disease progression in PTX + BEV 1st-line treatment for TNBC patients.

STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model

Background The development of the targeted signal transduction inhibitor STI571 has prompted us to treat chronic myeloid leukemia in different ways. Since STI571 may reverse multidrug-resistance of K562/MDR cells in vitro, we studied the effect of STI571 on multidrug-resistant K562 cells in vivo. Methods Multidrug-resistant human leukemia cell line K562-n/VCR expresses both bcr/abl fusion gene and multi-drug resistance （mdrl） gene. It is a vincristine resistant cell line subcloned from the vincristine （VCR） sensitive cell line K562-n induced by vincristine in vitro. K562-n and K562-n/VCR cells were inoculated subcutaneously into both sides of nude mice breast （5×10^6 cells/each） to establish a human leukemia xenograft model. The incidence and volume of tumor were observed. In the tumor-bearing nude mice, anti-tumor drugs vincristine, daunorubicin （DNR）, STI571, and STI571 plus VCR for the treatment of mdrl and bcr/abl double positive leukemia were studied respectively. Results The tumor incidence was 100% in the nude mice inoculated with either K562-n or K562-n/VCR. The transcription of the mdrl gene and expression of P-gp were negative in K562-n cells but positive in K562-n/VCR cells. The intracellular accumulation of DNR in K562-n cells was higher than that in K562-n/VCR cells （P〈0.05） The tumor incidence of K562-n/VCR cells in nude mice was much higher than that of K562-n cells in chemotherapy groups, and the mean volume of the tumors was also larger （P〈0.05）. STI571 combined with VCR significantly suppressed the proliferation of K562-n/VCR cells. Conclusions The MDR characteristics of K562-n/VCR in vivo were the same as in vitro. STI571 had a significant tumor-suppressing effect on VCR-sensitive leukemia ceils and a moderate effect on MDR leukemia cells. VCR combined with STI571 had an excellent tumor-suppressing effect on both K562-n/VCR and K562-n in the human-nude mice xenograft model.

SPA: A Quantitation Strategy for MS Data in Patient-derived Xenograft Models

With the development of mass spectrometry(MS)-based proteomics technologies,patient-derived xenograft(PDX),which is generated from the primary tumor of a patient,is widely used for the proteome-wide analysis of cancer mechanism and biomarker identification of a drug.However,the proteomics data interpretation is still challenging due to complex data deconvolution from the PDX sample that is a cross-species mixture of human cancerous tissues and immunodeficient mouse tissues.In this study,by using the lab-assembled mixture of human and mouse cells with different mixing ratios as a benchmark,we developed and evaluated a new method,SPA(shared peptide allocation),for protein quantitation by considering the unique and shared peptides of both species.The results showed that SPA could provide more convenient and accurate protein quantitation in human–mouse mixed samples.Further validation on a pair of gastric PDX samples(one bearing FGFR2 amplification while the other one not)showed that our new method not only significantly improved the overall protein identification,but also detected the differential phosphorylation of FGFR2 and its downstream mediators(such as RAS and ERK)exclusively.The tool pdx SPA is freely available at https://github.com/LiLab-Proteomics/pdx SPA.

Advances in prostate cancer research models:From transgenic mice to tumor xenografting models

The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes.

Murine models based on acute myeloid leukemia-initiating stem cells xenografting

Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.

Unwanted disorders and xenogeneic graft-versus-host disease in experimental immunodeficient mice:How to evaluate and how to report

Human-derived tumor models are essential for preclinical development of new anti-cancer drug entities.Generating animal models bearing tumors of human origin,such as patient-derived or cell line-derived xenograft tumors,is dependent on immuno-deficient strains.Tumor-bearing immunodeficient mice are susceptible to develop-ing unwanted disorders primarily irrelevant to the tumor nature;and if get involved with such disorders,reliability of the study results will be undermined,inevitably con-founding the research in general.Therefore,a rigorous health surveillance and clinical monitoring system,along with the establishment of a strictly controlled barrier facility to maintain a pathogen-free state,are mandatory.Even if all pathogen control and biosafety measures are followed,there are various noninfectious disorders capable of causing tissue and multiorgan damage in immunodeficient animals.Therefore,the re-searchers should be aware of sentinel signs to carefully monitor and impartially report them.This review discusses clinical signs of common unwanted disorders in experi-mental immunodeficient mice,and how to examine and report them.

Berberine retarded the growth of gastric cancer xenograft tumors by targeting hepatocyte nuclear factor 4α

BACKGROUND Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China.Despite advances in prevention,diagnosis,and therapy,the absolute number of cases is increasing every year due to aging and the growth of high-risk populations,and gastric cancer is still a leading cause of cancer-related death.Gastric cancer is a consequence of the complex interaction of microbial agents,with environmental and host factors,resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways.Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers.Trastuzumab,a monoclonal antibody against the HER2 receptor,is approved in the first-line treatment of patients with HER2+tumors,which accounts for 13%-23%of the gastric cancer population.Ramucirumab,a monoclonal antibody against VEGFR2,is currently recommended in patients progressing after first-line treatment.Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with dis-appointing results,such as anti-EGFR and anti-MET monoclonal antibodies.Therefore,it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets.AIM To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α(HNF4α)-WNT5a/β-catenin pathways played in the antitumor effects of berberine.METHODS MGC803 and SGC7901 subcutaneous xenograft models were established.The control group was intragastrically administrated with normal saline,and the berberine group was administrated intragastrically with 100 mg/kg/d berberine.The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction.The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors.Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.Western blotting and IHC were performed to assess the protein expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.RESULTS In the both MGC803 and SGC7901 xenograft tumor models,berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors.In the SGC7901 and MGC803 subcutaneously transplanted tumor models,berberine down-regulated the expression of HNF4α,WNT5a andβ-catenin in tumor tissues from both transcription and protein levels.Besides,berberine also suppressed the protein expression of HNF4α,WNT5a andβ-catenin in liver tissues.CONCLUSION Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors,and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/β-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models.

Evolution of Tumor Model: From Animal Model of Tumor to Tumor Model in Animal

Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the “model” system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.

An improved model of heterotopic cardiac xenotransplantation from guinea－pig to rat

Shortage of allogenic donor heart remains a serious problem all over the world leading to an upsurge in the study of xenografic cardiac transplantation. This study, based on the cuff technique, modified the grafting procedure in some aspects and successfully established a model of cervical cardiac xenotransplantation from guinea-pig to rat. Of 112 xenografting procedures performed in this group, the success rate of operation was 98. 2%, with only 2 cases of operative failure. Mean survival of the xenografts was 14±5. 5 min. The result showed that the modified model is more available and reproducible with much less bleeding than the original model, thus providing a more practical and stable experimental model for studying the mechanisms of hyperacute vascular rejection and the prevention of rejection in discordant cardiac xenotransplantation.

头颈部恶性肿瘤研究模型的演化

恶性肿瘤发生发展的机制探索以及抗癌药物治疗疗效的评估均有赖于各种体内与体外研究模型的建立。近几十年间,随着生物医学技术的快速发展,恶性肿瘤的体内外研究模型也发生了巨大的变化。基因检测技术从单基因到多基因的进展促进了生物信息学飞速发展和恶性肿瘤概念的转变;体外细胞研究模型从单层的二维培养、原代培养向立体的三维构型发展,从而更好地重现肿瘤组织的细胞间交互作用与功能;体内动物研究模型由传统的致癌物诱导、细胞或组织形成移植瘤逐渐演变为基因编辑的动物模型或人源性肿瘤异种移植模型,从而可以针对性地研究相关基因在肿瘤发生发展中的作用;传统的临床研究也从简单的临床回顾性研究更多地向前瞻性研究转变,Ⅰ期/Ⅱ期/Ⅲ期临床研究,研究者发起的临床研究以及真实世界临床研究,这些研究为临床研究增添了活力。目前恶性肿瘤研究模型存在的主要不足包括模型的单一性、对肿瘤微环境的模拟不足、动物肿瘤模型与人类肿瘤差异性,以及缺乏对个性化医疗的考量。未来仍需要进一步研发和优化研究模型,并更有效地将不同模型整合起来,形成一个优化的整体实验模型系统。本文将系统回顾恶性肿瘤研究模型的演化并对相关模型进行阐述,为科研工作者进行恶性肿瘤的研究提供合理的研究模型。

人源性胰母细胞瘤异种移植模型的构建与验证

目的研究构建合适的动物模型用于胰母细胞瘤(PBL)的化疗药物筛选及新药评估。方法将手术切除的PBL肿瘤组织碎块移植到免疫缺陷的小鼠皮下组织,待移植瘤生长至1500 mm^(3)时进行瘤体传代及保存。使用HE染色、免疫组织化学及PCR法对成功建立的PBL患儿起源的异种移植(PDX)模型进行人源性鉴定。结果HE染色显示小鼠PDX中的肿瘤组织及细胞和患儿肿瘤细胞形态基本相同,免疫组化结果显示β-连环蛋白(β-Catenin)、细胞角蛋白7(CK7)和细胞角蛋白19(CK19)在PDX模型组织与人属源性肿瘤组织中有相同的免疫学特征。PCR分析显示PDX组织和原发肿瘤组织具有相同的个体来源。结论所建立胰母细胞瘤来源PDX高度保留了原发胰母细胞瘤的生长模式及蛋白表达特性,为胰母细胞瘤患者的基础研究和临床用药指导提供了重要的实验模型工具,给推动疾病机制探索及制定个性化治疗方案提供了科学依据。

肺癌脑转移瘤人源异种移植模型的构建及应用研究进展

肺癌脑转移瘤是中枢神经系统最为常见的继发性恶性肿瘤,目前共识的治疗方式是在安全范围内通过手术最大程度切除肿瘤组织,术后进行化学治疗以及局部或全身放射治疗,但其治疗效果仍不理想。人源异种移植瘤模型能够很好地保留患者原发肿瘤异质性、组织学特性和分子多样性,能够为研究新的治疗方法提供新思路及新的研究工具。本文就移植瘤模型的建立、模型在肺癌脑转移瘤治疗中的应用研究以及模型的应用前景和局限性进行综述。

肺癌小鼠模型研究进展

肺癌是世界上发病率和死亡率最高的恶性肿瘤之一,明确其病因、发病机制及药物防治方法是目前研究热点。小鼠是肺癌临床前研究中最常用的实验动物,根据不同的研究策略和目的选择合适的小鼠模型。目前常用的小鼠肺癌模型包括诱发性模型、移植物模型及基因工程模型等,根据研究目的选择不同的小鼠模型。回顾国内外肺癌小鼠模型相关文献报道,归纳总结常用肺癌小鼠模型的研究进展,为肺癌研究提供参考。

半胱氨酸蛋白酶抑制剂1对人食管鳞状细胞癌斑马鱼移植瘤模型的作用

目的通过构建人食管鳞状细胞癌(ESCC)的斑马鱼移植瘤模型,研究半胱氨酸蛋白酶抑制剂1(CST1)表达对ESCC肿瘤转移及血管生成的影响。方法通过慢病毒转染技术构建CST1过表达/敲低ESCC细胞,并经Transwell小室法检测细胞侵袭/迁移能力的变化,再通过显微注射技术分别将CST1过表达/敲低ESCC细胞注射至斑马鱼胚胎卵黄囊,建立人ESCC斑马鱼移植瘤模型,观察两株细胞在斑马鱼体内的定植迁移、分布及对斑马鱼肠下静脉丛(SIVs)的影响。结果体外实验表明,CST1过表达ESCC细胞的侵袭/迁移能力明显增强,而CST1敲低ESCC细胞的侵袭/迁移能力明显减弱。斑马鱼移植瘤模型实验表明,当接种细胞数为300~500个/只时,ESCC斑马鱼移植瘤建模的存活率大于0.8;与对照组相比,CST1过表达细胞在斑马鱼体内具有明显的迁移特性,且SIVs区域血管呈明显增生状态,而CST1敲低细胞迁移能力减弱,SIVs区域血管生成明显受到抑制。结论通过显微注射技术成功构建人ESCC的斑马鱼异种移植瘤模型,并应用于肿瘤的在体功能学研究。CST1过表达具有促进ESCC肿瘤转移及血管生成的作用,提示CST1在ESCC发生发展进程中发挥潜在的致癌作用。

转导蛋白β样1X连接受体1表达对卵巢癌A2780细胞增殖和迁移的影响

目的:研究转导蛋白β样1X连接受体1(transducin beta-like 1X-linked receptor,TBL1XR1)在卵巢癌患者组织中表达,及其对卵巢癌A2780细胞增殖和迁移的影响。方法:采用实时荧光定量PCR(qRT-PCR)检测10对卵巢癌组织、癌旁组织中及人卵巢癌IOSE80、A2780、CP70、SKOV-3中TBL1XR1 mRNA表达,筛选TBL1XR1 mRNA高表达细胞株。选择4~6周龄雌性BALB/C裸鼠,建立卵巢癌人源肿瘤异种移植(patient-derived tumor xenografts,PDTX)模型;将10只模型鼠均分为siR-NC组和si-TBL1XR1组,每组5只,分别给予siR-NC、si-TBL1XR1局部注射,10 mg/kg,每3 d注射1次,18 d后取各组瘤组织,计算其体积与重量。取卵巢癌A2780细胞,将其分为siR-NC组、si-TBL1XR1组、pcDNA3.1组和pcDNA3.1-TBL1XR1组,分别予以siR-NC、si-TBL1XR1、pcDNA3.1空载质粒和pcDNA3.1-TBL1XR1质粒处理;采用蛋白免疫印迹法检测各组卵巢癌细胞周期蛋白表达,MTT比色法检测细胞活力,流式细胞术检测细胞周期和凋亡细胞比例,以及Transwell细胞迁移实验检测细胞迁移能力。结果:卵巢癌组织中TBL1XR1 mRNA表达明显高于癌旁组织(P<0.05);人卵巢癌A2780细胞系TBL1XR1 mRNA表达明显高于卵巢癌IOSE80、CP70、SKOV-3细胞系(P<0.05)。与siR-NC组相比,第18天si-TBL1XR1组瘤体积明显减小(P<0.05),重量明显降低(P<0.05)。与siR-NC组相比,si-TBL1XR1组促癌细胞周期蛋白表达明显降低(P<0.05),与pcDNA3.1组相比,pcDNA3.1-TBL1XR1组表达则明显升高(P<0.05);与siR-NC组相比,si-TBL1XR1组卵巢癌细胞迁移数明显降低(P<0.05),早期凋亡和晚期凋亡细胞比例明显升高(P<0.05);与pcDNA3.1组相比,pcDNA3.1-TBL1XR1组卵巢癌细胞迁移数明显增多(P<0.05),早期凋亡和晚期凋亡细胞比例明显降低(P<0.05)。结论:TBL1XR1在卵巢癌组织中呈高表达,降低TBL1XR1 mRNA表达可抑制卵巢癌A2780细胞增殖和迁移。