目的 分析TIMELESS、鼠肉瘤病毒家族相关蛋白2A（RAB2A）、异常纺锤体样小头畸形相关基因（ASPM）在乳腺癌组织中的表达及与临床特征相关性。方法 选取2019年2月—2021年2月我院乳腺癌组织标本84例作为研究组、正常乳腺组织标本53例作为对照组,采用荧光定量聚合酶测定TIMELESS、ASPM,采用Western blot检测RAB2A蛋白表达情况,分析上述三个指标在乳腺癌中表达及与临床特征相关性。结果 对比对照组,研究组TIMELESS、ASPM表达较高,RAB2A较低（P<0.05）。TIMELESS、RAB2A、ASPM与乳腺癌淋巴结浸润、TNM分期、分化程度相关（P<0.05）。TIMELESS、RAB2A、ASPM为影响乳腺癌发生的危险因素（P<0.05）。TIMELESS、RAB2A负相关（r=-0.383、P=0.001）;TIMELESS、ASPM正相关（r=0.397、P=0.001）;RAB2A、ASPM负相关（r=-0.257、P=0.018）。对比TIMELESS、RAB2A、ASPM单一检测,三者联合检测对乳腺癌的诊断价值较高（P<0.05）。结论 乳腺癌患者TIMELESS、ASPM呈高表达,RAB2A呈低表达,上述三个指标与乳腺癌高度相关,可作为乳腺癌发生的检测指标。

Objective To analyze the expression of TIMELESS,murine sarcoma virus family related protein 2A（RAB2A）and abnormal spindle like microcephaly related gene（ASPM）in breast cancer tissues and their correlation with clinical features．Methods A total of 84 breast cancer tissue samples from our hospital from February 2019 to February 2021 were selected as the study group and 53 normal breast tissue samples were selected as the control group．Time,ASPM and RAB2A protein expression were determined by fluorescent quantitative polymerase,and RAB2A protein expression was detected by Western blot．The expression of the above three indicators in breast cancer and their correlation with clinical characteristics were analyzed．Results Compared with the control group,the study group had higher TIMELESS and ASPM expression levels and lower RAB2A level（P<0.05）．TIMELESS,RAB2A and ASPM expressions were correlated with lymph node infiltration,TNM stage and differentiation of breast cancer（P<0.05）．TIMELESS,RAB2A and ASPM were the risk factors of breast cancer（P<0.05）．TIMELESS and RAB2A were negatively correlated（r=-0.383,P=0.001）;TIMELESS and ASPM were positive correlated（r=0.397、P=0.001）;RAB2A and ASPM were negatively correlated（r=-0.257,P=0.018）．Compared with the single detection of TIMELESS,RAB2A and ASPM,the combined detection had higher diagnostic value for breast cancer（P<0.05）．Conclusions Patients with breast cancer had high expression of TIMELESS and ASPM,and low expression of RAB2A．The above three indicators were highly correlated with breast cancer and can be detection indicators for breast cancer．

目的 构建尺寸可变纳米递送系统PAMAM/DOX-pep并进行表征,检测其理化性质并评价其体外抗肿瘤效果与靶向性。方法 将阿霉素（DOX）物理包埋在阳离子聚合物PAMAM的疏水空腔内,以4-（N-马来酰亚胺基甲基）环己烷羧酸N-羟基琥珀酰亚胺酯（SMCC）作为交联剂,采用金属基质蛋白酶（MMP-2）敏感的多肽pep（CPLGVRGC）串联小粒径纳米颗粒形成大尺寸纳米递送系统（PAMAM/DOX-pep）,对各纳米颗粒的粒径、电位、理化性质以及对小鼠乳腺癌细胞（4T1）的抑制作用、细胞摄取效果和核靶向作用进行检测。结果 PAMAM/DOX粒径约为10 nm,载药率为23%,多肽pep交联后形成的PAMAM/DOX-pep粒径约为200 nm,可在低pH下缓释DOX,7天内体外保持稳定且溶血率低、安全无毒,其与MMP-2共孵育后细胞摄取量与核靶向性显著增加。结论 尺寸可变纳米颗粒有助于克服尺寸所引发的递送障碍,将药物靶向递送至乳腺癌细胞核内并发挥作用,为纳米递送系统的设计提供了新策略。

Objective To construct and characterize the size-variable nano-delivery system PAMAM/DOX-pep,examine its physicochemical properties and evaluate its antitumor and targeting effects in vitro. Methods Small particle size PAMAM/DOX was obtained by physically encapsulating DOX within the hydrophobic cavity of the cationic polymer PAMAM. The large size nano-delivery system(PAMAM/DOX-pep)was formed by tandem linking small size nanoparticles by MMP-2 sensitive peptide pep(CPLGVRGC)using SMCC as a cross-linker. The particle size,potential,physical and chemical properties,inhibitory effect,cell uptake and nuclear targeting effect of each nanoparticle on mouse breast cancer cells(4T1)were detected. Results The particle size of PAMAM/DOX was about 10 nm,and the drug loading rate was 23%. PAMAMAM/DOX-pep,formed after cross-linking of peptide,had a particle size of about 200 nm,which could release DOX slowly at low pH,and remained stable,safe and non-toxic in vitro for 7 days with low hemolysis rate,and its cellular uptake amount and nuclear targeting rate increased significantly after co-incubation with MMP. Conclusions Size-variable nanoparticles overcome size-induced delivery barriers to target and deliver drugs to the 4T1 nucleus,providing a new strategy for the design of nano delivery systems.

目的 探讨柚皮素对人乳腺癌细胞株MCF-7和小鼠乳腺癌细胞系4T1的作用机制。方法 选择人乳腺癌细胞株MCF-7和小鼠乳腺癌细胞系4T1为实验对象,设置对照组和柚皮素组,其中柚皮素组分为20、40、80 和120 μmol/L 4个浓度,利用CCK-8、平板克隆形成实验检测柚皮素对乳腺癌细胞的增殖作用,应用流式细胞术检测柚皮素对乳腺癌细胞的凋亡作用。建立乳腺癌移植瘤模型,应用柚皮素作用于模型小鼠,探讨柚皮素在体内抗肿瘤作用。通过荧光定量PCR和蛋白免疫印迹实验检测自噬相关基因,分析其作用机制。结果 经柚皮素处理后,乳腺癌细胞的增殖明显受到抑制,正常乳腺癌细胞增殖情况变化不大,MCF-7乳腺癌细胞和小鼠乳腺癌4T1均出现明显的凋亡（P<0.001）。结论 柚皮素可以抑制乳腺癌细胞的增殖,且对正常乳腺细胞无明显毒副作用。柚皮素通过凋亡和自噬方式促进乳腺癌细胞的死亡,体内实验结果显示柚皮素具有抗肿瘤作用,并可促进其坏死。

目的 观察程序性死亡受体1（PD-1）联合细胞毒性T淋巴细胞相关蛋白4（CTLA-4）双免疫疗法对改善晚期乳腺癌近期疗效及远期预后的影响。方法 选择2020年5月—2022年5月商丘市第一人民医院收治的124例晚期乳腺癌患者为研究对象,经随机数字表法将其分为对照组（60例）和观察组（64例）,对照组予以常规PD-1单抗免疫疗法治疗,观察组采用PD-1联合CTLA-4双免疫疗法治疗,比较2组患者治疗前后肿瘤标志物水平、治疗后病灶缓解情况,对所有患者开展为期1年随访,统计并对比2组的不良反应发生情况及远期生存情况。结果 治疗前,2组患者的肿瘤标志物水平比较差异均无统计学意义（均P>0.05）;治疗后,观察组的癌胚抗原为（3.36±0.17）ng/mL,糖类抗原15-3为（25.33±5.28）U/mL,糖类抗原19-9为（38.77±5.62）U/mL,均低于对照组[（5.27±1.36）ng/mL、（28.44±5.18）U/mL、（41.25±5.46）U/mL,均P<0.05]。治疗后,观察组的完全缓解率为21.88%（14/64）,部分缓解率为31.25%（20/64）,病情稳定率为37.50%（24/64）,均高于对照组[8.33%（5/60）、13.33%（8/60）、23.33%（14/60）],肿瘤生长率为（30.27±5.18）%,肿瘤超进展率为6.25%（4/64）,均低于对照组[（33.49±5.32）%、18.33%（11/60）,均P<0.05]。治疗后,观察组的不良反应发生率为34.38%（22/64）,略高于对照组33.33%（20/60）,组间比较差异无统计学意义（P>0.05）;观察组的中位无进展生存期为（9.33±2.25）月,中位总生存期为（10.76±3.32）月,均高于对照组[（7.25±2.31）月、（7.41±1.62）月,均P<0.05]。结论 PD-1联合CTLA-4双免疫疗法能有效改善晚期乳腺癌的近期疗效及远期预后,此疗法未明显增加不良反应发生风险,安全性高。

Objective To observe the effect of programmed cell death protein-1（PD-1）combined with cytotoxic T lymphocyte-associated antigen-4（CTLA-4）dual immunotherapy on the short-term efficacy and long-term prognosis of advanced breast cancer．Methods A total of 124 patients with advanced breast cancer who were admitted to the First People's Hospital of Shangqiu City from May 2020 to May 2022 were selected as the research objects．They were randomly divided into the control group（60 cases）and the observation group（64 cases）by the method of random number table．The control group was treated with conventional PD-1 monoclonal antibody immunotherapy,and the observation group was treated with PD-1 combined with CTLA-4 double immunotherapy．The levels of tumor markers before and after treatment and the focal remission after treatment were compared between the two groups．All patients were followed up for one year,the incidence of adverse reactions and long-term survival between the two groups were compared．Results Before treatment,there was no statistically significant difference in the levels of tumor markers between two groups（all P>0.05）．After treatment,the carcino-embryonic antigen content of the observation group was（3.36±0.17）ng/mL,CA153 was（25.33±5.28）U/mL,and CA199 was（38.77±5.62）U/mL,which were lower than those of the control group [（5.27±1.36）ng/mL,（28.44±5.18）U/mL,（41.25±5.46）U/mL,all P<0.05]．After treatment,the complete remission rate of the observation group was 21.88%（14/64）,partial remission rate was 31.25%（20/64）,and stable disease rate was 37.50%（24/64）,all higher than those of the control group [8.33%（5/60）,13.33%（8/60）,23.33%（14/60）];tumor growth rate of the observation group was（30.27±5.18）%,hyper progressive disease rate was 6.25%（4/64）,both lower than those of the control group [（33.49±5.32）%,18.33%（11/60）,both P<0.05]．After treatment,the incidence of adverse reactions in the observation group was 34.38%（22/64）,slightly higher than that in the control group 33.33%（20/60）（P>0.05）．The median progression free survival of the observation group was（9.33±2.25）months,and the median overall survival was（10.76±3.32）months,both higher than those of the control group [（7.25±2.31）months and（7.41±1.62）months]（P<0.05）．Conclusions PD-1 combined with CTLA-4 dual immunotherapy can effectively improve the short-term efficacy and long-term prognosis of advanced breast cancer．This therapy does not significantly increase the risk of side effects,which is safe．

目的 探讨核结合蛋白2(NUCB2)介导的下游信号分子和通路,为阐明NUCB2在乳腺癌中的功能提供依据。方法 构建NUCB2-RNAi慢病毒载体,感染MDA-MB-231细胞株。然后将MDA-MB-231分为阴性对照病毒感染细胞组(NC组)、感染NUCB2基因shRNA病毒细胞组(KD组),用Affymetrix基因表达谱芯片对NUCB2下游基因进行筛选,并对所有数据进行独创性通路分析(IPA)分析。用qPCR测定mRNA水平。统计采用SPSS 20.0软件。结果 Path-Array研究筛选了KD组与NC组的差异基因,其中上调基因186个,下调基因356个,部分差异表达基因的检测表明,这些基因的mRNA水平与Path-Array筛选结果一致。IPA分析显示,经典途径中差异表达基因的显著富集表明胆固醇生物合成的超途径被显著抑制。上游调节因子分析显示了所有不同表达基因的上游调节因子,包括转录因子、细胞因子、小RNA、受体、激酶、化学分子和药物。疾病和功能差异表达基因的显著丰富表明,与NUCB2相关的差异表达基因与41种疾病和功能显著相关,更多与癌症、组织损伤和异常相关。结论 NUCB2的功能涉及多种基因和多种信号通路。

Objective In order to further explore the downstream signal molecules and pathways mediated by nucleobindin-2 (NUCB2), to provide a basis for elucidating the significance of NUCB2 in breast cancer. Method NUCB2-RNAi lentivirus vector was constructed and infecting MDA-MB-231 cell line.Then MDA-MB-231 cells were divived into two group, cells with negative control virus infection (NC group) and cells infected with NUCB2 gene shRNA virus (KD group). NUCB2 downstream gene screening was conducted by Affymetrix gene expression profiling Path-Array chip and all data were analyzed by ingenuity pathway analysis (IPA). The mRNA level was detected by qPCR. SPSS 20.0 software was used for statistics. Results Path-Array study screened out differential genes between KD and NC group which the number of up-regulated genes was 186, the number of down-regulated genes was 356.Detection of some differentially expressed genes showed that the mRNA levels of these genes were consistent with the results of Path-Array screening.IPA analysis revealed that significant enrichment of differentially expressed genes in the classical pathway showed superpathway of cholesterol biosynthesis was significantly inhibited.The upstream regulatory factor analysis showed the upstream regulatory factors of all the differentially expressed genes, including transcription factors, cytokine, small RNA, receptors, kinases, chemical molecules and drugs.The significant enrichment of differentially expressed genes in disease and function showed that NUCB2 associated differentially expressed genes were significantly related with 41 diseases and functions, which were more related with cancer, organismal injury and abnormities. Conclusion The function of NUCB2 involved multiple genes and multiple signaling pathways.

目的 乳腺癌是世界范围内最常见的恶性肿瘤之一。目前,人们对乳腺癌的发病机制进行了大量的研究,但对其分子机制的认识尚不清楚。本研究采用生物信息学技术,筛选乳腺癌潜在的关键基因,最终为乳腺癌的诊断、治疗及预后判断提供潜在的生物标记物。方法 从基因表达综合数据库(GEO)下载基因芯片GSE36295、GSE71053和GSE86374,通过GEO2R鉴定差异表达基因(DEGs),并进行功能富集分析。利用STRING构建了蛋白质-蛋白质相互作用网络(PPI),并采用Cytoscape进行了模块分析。结果 共鉴定出95个DEGs,包括62个上调基因和33个下调基因。共鉴定出10个Hub基因:CENPF、KIF2C、TOP2A、NUSAP1、HMMR、MELK、KIF4A、ASPM、CEP55、CCNB1。结论 本研究发现的Hub基因可能对乳腺癌的发展和预后存在一定影响,为乳腺癌的诊断和治疗提供候选靶点。

Objective Breast cancer is one of the most common cancers worldwide. At present, a lot of researches have been carried out on the pathogenesis of breast cancer, but the molecular mechanisms of breast cancer are still not well understood. In this study, bioinformatics technology was used to screen the potential key genes of breast cancer, and ultimately to provide potential biomarkers for the diagnosis, treatment and prognosis of breast cancer. Methods The microarray datasets GSE36295、GSE71053和GSE86374 were downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified by GEO2R, and the enriched functions and pathways of the DEGs were analyzed. Protein-protein interaction network (PPI) was constructed by using String, and the module analysis was performed using Cytoscape. Results A total of 95 DEGs were identified, consisting of 62 upregulated genes and 33 downregulated genes.Ten hub genes were identified: CENPF,KIF2C,TOP2A,NUSAP1,HMMR,MELK,KIF4A,ASPM,CEP55,CCNB1. Conclusion The hub gene was found in this study may be involved in the development and prognosis of breast cancer. It may provide candidate targets for diagnosis and treatment of breast cancer.

目的 分析晚期三阴性乳腺癌(TNBC)的危险因素并建立有效的预后列线图。方法 通过检索美国SEER(surveillance, epidemiology, and end results)数据库筛选晚期TNBC患者,采用单因素和多因素分析来确定晚期TNBC的独立预后因素,并以此构建了列线图,通过校准曲线检验和C指数(C-index)评估已建立的列线图。结果 共纳入4 687例晚期TNBC患者,与同期其他分子分型的乳腺癌相比较,TNBC的预后最差。单因素分析发现,年龄、性别、分期、手术、化疗、放疗、转移与更好的预后相关(P<0.05)。多因素分析发现年龄、性别、种族、分期、手术、化疗、放疗、各器官转移是患者预后的独立影响因素(P<0.05),并以此构建了列线图,其C-index为0.75(95％CI,0.71～0.79),校准图显示了预测的总生存期(OS)与观察到的OS之间的最佳一致性。结论 我们分析了晚期TNBC的临床特征,为TNBC患者的OS提供了一些预后因素,并根据这些预后因素制定了列线图,帮助临床医生进行风险管理并选择TNBC患者的长期生存策略。

Objective To analyze the risk factors of advanced triple-negative breast cancer (TNBC) and establish an effective prognostic nomogram. Methods Screening patients with advanced TNBC by searching the SEER (surveillance, epidemiology, and end results) database, using univariate and multivariate analysis to determine the independent prognostic factors of advanced TNBC, and constructing a nomogram based on it. Results A total of 4 687 patients with advanced TNBC were included. Compared with other types of breast cancer over the same period, TNBC had the worst prognosis. Univariate analysis found that age, gender, stage, surgery, chemotherapy, radiotherapy, and metastasis were associated with a better prognosis (P<0.05). Multivariate analysis found that age, gender, race, stage, surgery, chemotherapy, radiotherapy, and metastasis of the organs were independent factors affecting the prognosis of patients (P<0.05), and constructed a nomogram with a C-index of 0.75 ( 95% CI, 0.71～0.79). The calibration chart showed the best agreement between the predicted overall survival (OS) and the observed OS. Conclusion We analyzed the clinical features of advanced TNBC, provided some prognostic factors for the OS of TNBC patients, and developed a nomogram based on these prognostic factors to help clinicians manage risk and choose long-term survival strategies for TNBC patients.

目的 观察乳腺癌术后辅助化疗联用槐耳颗粒对内分泌激素及生存期的影响。方法 选取我院肿瘤科于2016年7月—2019年7月进行乳腺癌治疗术的80例乳腺癌患者,将患者按照随机数表法分为观察组与对照组,两组各40例。两组患者均给予预防性止吐等常规治疗,对照组予以表柔比星联合紫杉醇静脉注射,观察组在对照组的基础上给予槐耳颗粒,两组患者均治疗6个月,对比两组患者治疗3个月后血清黄体生成素(LH)、卵泡雌激素(FSH)、雌二醇(E₂),对比两组患者生存时间、无疾病进展生存期及1年生存率。结果 观察组与对照组LH、FSH、E₂水平对比均P＜0.05。在治疗后通过电话、视频等对所有患者进行随访,随访期间两组患者均无失访,生存时间、无疾病进展生存期、1年生存率对比均有P＜0.05。结论 在乳腺癌术后辅助化疗期联用槐耳颗粒可有效改善内分泌激素指标,并使生存时间获益。

Objective To observe the effect of adjuvant chemotherapy combined with Huaier granule on endocrine hormone and survival time after breast cancer operation. Methods A total of 80 cases of breast cancer patients underwent breast cancer treatment in the oncology department of our hospital from July 2016 to July 2019 were selected and divided into two groups according to the random number table method. The control group and the observation group had 40 cases each.Two groups of patients were given preventive anti-nausea and other conventional treatment, the control group was treated with epirubicin and paclitaxel intravenous injection, the observation group was treated with Huaier granuleon the basis of treatment of the control group, two groups of patients were treated for 6 months.The serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E₂) were compared between the two groups after 3 months of treatment. The survival time, progression free survival and 1-year survival rate of the two groups were compared. Results The levels of LH, FSH and E₂ in the comparison between two groups were all P<0.05.After treatment, all patients were followed up by telephone or video. During the follow-up period, there was no loss of follow-up in the two groups. The survival time, progression free survival and 1-year survival rate of the two groups were all P<0.05. Conclusion Huaier granule can effectively improve endocrine hormone indexes and survival time in adjuvant chemotherapy period after breast cancer surgery.

目的 回顾性分析因化疗需要行完全植入式输液港的乳腺癌患者相关血栓形成的因素。方法 收集广州市第一人民医院乳腺外科2018年5月—2019年4月期间行植入式输液港置入术的60例乳腺癌患者相关资料,采用SPSS 26.0软件进行统计学分析。结果 输液港相关血栓形成(catheter related thrombosis,CRT)发生率为21/60(35%)。BMI≤24的患者CRT发生率为30.3%,BMI＞24则为40.74%;行4、6、8次化疗的CRT发生率分别为20%、33.34%、44.12%,导管末端位于T5-T8的CRT发生分别为:66.67%, 26.09%, 28.57%, 50%;Ki-67高表达的血栓发生率为27.5%,低Ki-67表达则为50%;导管材质为聚氨酯的血栓发生率为47.62%,硅胶材质则为28.21%,但差异均无统计学意义(P＞0.05)。雌激素受体/孕激素受体(estragen receptor/progesterone receptor,ER/PR)阴性的CRT发生率为60%,ER/PR阳性则为23.8%(P＜0.05);人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)阳性CRT发生率为50%,HER-2阴性CRT发生率则为23.53%(P＜0.05)。多因素分析:相对于ER/PR阳性,ER/PR阴性将增加CRT的发生(OR=4.482, 95%CI:1.116～17.998, P＜0.05);Ki-67的表达对血栓形成的影响具有统计学意义(OR=7.051, 95%CI:1.513～32.858, P＜0.05);HER-2表达对CRT的形成均无统计学意义(OR=0.254,95%CI:0.058～1.115, P＞0.05)。结论 血栓形成是植入式输液港术后常见的并发症,与肿瘤ER/PR表达相关,临床上应得到重视。

Objective To analyse the factors that lead to venous thrombosis among breast cancer patients who need totally implantable access port(TIAP) for chemotherapy. Methods Collecting the clinical data of 60 breast patients admitted to Guanzhou First People's Hospital from May 2018 to April 2019, analysed with SPSS 26.0. Results Catheter-related thrombosis(CRT) occurred in 21 out of 60(35%) patients with TIAP. 30.3% patients with BMI≤24 and 40.74% patients with BMI＞24 had CRT, and incidences of CRT were 20%, 33.34%, 44.12% at the fourth, sixth, eighth therapy respectively. The access terminal position at T5-T8 had 66.67%, 26.09%, 28.57%, 50% of incidence for CRT respectively. 27.5% CRT was with high Ki-67 expression and 50% CRT was with low Ki-67 expression; 47.62% patients with polyurethane catheter and 28.21% patients with silicone catheter got CRT. There were no significant differences in the comparisons above. CRT incidence in ER/PR negative patients was 60%,while 23.08% in ER/PR positive patients (P＜0.05). In HER-2 positive and negative patients, the incidences of CRT were 50% and 23.53% (P＜0.05). Logistic regression noticed that ER/PR negative would increase the incidence of CRT(OR=4.482, 95%CI:1.116～17.998, P＜0.05), low Ki-67 expression would accelerate CRT(OR=7.051, 95%CI:1.513～32.858, P＜0.05). There was no significant difference in the formation of CRT with HER-2 expression(OR=0.254, 95%CI:0.058～1.115, P＞0.05). Conclusion CRT was a common complication of TIAP, which related with ER/PR expression, and should pay attention to during clinical practices.

目的 探究超声-微泡介导的miR-128通过调节PTEN对乳腺癌细胞阿霉素耐药的影响。方法 qPCR检测miR-128在乳腺癌细胞系中的表达,并利用结合微泡的miR-128质粒(质粒+超声+SF6微泡)转染细胞,探究超声-微泡介导的miR-128对乳腺癌细胞阿霉素耐药的影响。CCK8实验检测乳腺癌细胞的活性;qPCR检测过表达miR-128后对PTEN的影响和对乳腺癌细胞阿霉素耐药的影响。结果 miR-128在阿霉素耐药乳腺癌细胞中低表达;过表达miR-128能够增加乳腺癌细胞对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性;miR-128通过调节PTEN从而促进乳腺癌细胞对阿霉素耐药。结论 miR-128过表达可以增强乳腺癌对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性,本研究为乳腺癌阿霉素耐药的治疗提供了新的分子靶标和治疗途径。

Objective To explore the effect of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in breast cancer cells by regulating PTEN. Methods Quantitatine PCR (qPCR) was used to detect the expression of miR-128 in breast cancer cell lines, and the ultrasound-microbubble combined miR-128 plasmid(plasmid+ultrasound+SF6 microbubbles) was used to transfect the cells to explore the effects of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in cancer cells. The CCK8 experiment was used to detect the activity of breast cancer cells; qPCR was used to detect the effect of overexpression of miR-128 on PTEN and the effect on doxorubicin resistance of breast cancer cells. Results miR-128 was under-expressed in doxorubicin-resistant breast cancer cells; overexpression of miR-128 increased the sensitivity of breast cancer cells to doxorubicin,ultrasound-microbubble mediated miR-128 further enhanced breast cancer cells sensitivity to doxorubicin; miR-128 promote resistance to doxorubicin in breast cancer cells by regulating PTEN. Conclusion Overexpression of miR-128 could enhance the sensitivity of breast cancer to doxorubicin. Ultrasound-microbubble mediated miR-128 further enhanced the sensitivity. This study provided a treatment for doxorubicin resistance in breast cancer with new molecular targets and therapeutic approaches.