Comparative analysis of lung cancer with features of bronchioloalveolar carcinoma and other types of adenocarcinoma

Objective: The aim of this study was to investigate the clinicopathologic and prognostic factors of the partial subtypes of lung adenocarcinoma, including pure bronchioloalveolar carcinoma (BAC), adenocarcinoma (AC) with BAC component and AC without BAC component. Methods: One hundred and six adenocarcinoma specimens which were followed up completely for 3 years, were obtained from 106 patients (45 men and 61 women) who underwent surgical resection for pathologically confirmed pulmonary adenocarcinoma in the Cancer Hospital of Tianjin Medical University, from June 2004 to December 2005. According to the recent 2004 World Health Organization (WHO) pathological classification criteria of lung cancer, lung adenocarcinomas were divided into three subgroups: pure BAC, AC with BAC component and AC without BAC component. The clinical data were retrospectively analyzed based on statistical methods. All data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed, meanwhile, we conducted a Log-rank test. Results: The statistical analysis showed that no significant association was found among the three groups in gender and age; however, smoke index, tumor size, N stage, TNM stage, postoperative recurrence and metastasis had a statistically significant correlation among three groups (P < 0.01). The 3-year survival rates of the three groups were 96.4%, 61.0% and 40.5% respectively, which had a statistically significant difference. And the 3-year survival rate was significantly higher in the patients with pure BAC than in the patients with other types of lung adenocarcinomas (P < 0.01). In contrast to the other two groups (pure BAC and AC with BAC component), we found the evidence that the 3-year prognosis of lung adenocarcinoma without BAC component was worse than the two formers. Conclusion: The three groups (pure BAC, AC with BAC component and AC without BAC component) have their own distinct clinicopathologic features respectively and completely different clinical prognosis. The strict distinction of the subtypes of lung adenocarcinoma can provide more reliable basis for scientific and comprehensive clinical treatment and contribute to assess the clinical prognosis effectively.

Epidemiology of EGFR Mutation in Adenocarcinoma NSCLC Patients in India: A Systematic Review and Meta-Analysis

Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence of EGFR mutation epidemiology in Indian patients with adenocarcinoma (ADC) Non-Small Cell Lung Cancer (NSCLC). We conducted a structured literature search in PubMed, and EMBASE databases from January 2004 through October 2019. The primary outcome of interest was prevalence of EGFR mutation by gender, smoking status, and mutation subtype. The review included 34 studies. EGFR mutation prevalence was 39.5% in patients with ADC, and significantly higher in females, non-smokers, and patients with exon 19 deletions. The EGFR mutation frequency in Indian patients with ADC was higher than reported in Caucasians but at a lower range of that reported in East Asians. These findings support the use of EGFR mutation testing to guide choice of treatment.

Primary hepatoid adenocarcinoma of the lung in Yungui Plateau,China:A case report

BACKGROUND Hepatoid adenocarcinoma(HAC)occurs in extrahepatic organs such as the gastrointestinal tract,testes,ovaries,lungs,mediastinum and pancreas,and frequently produces a-fetoprotein(AFP).HAC of the lung(HAL)is rare,characterized by difficult treatment and poor prognosis.There are no reports of HAL in Yunnan-Guizhou Plateau,China.CASE S UMMARY A 60-year-old male patient was clinically diagnosed with HAL pT3 NOM0,stageⅡB.Chest computed tomography revealed a 7.5 cm x 7.2 cm soft tissue mass located in the right lung upper lobe and the adjacent superior mediastinum.Right upper lobectomy was performed.The diagnosis of HAL was confirmed by pathological examination,and the patient received paclitaxel and carboplatin as adjuvant chemotherapy after surgery.CONCL USION Clinical manifestations,pathological features,imaging findings,auxiliary examination,and treatment planning of HAL are presented to help clinicians improve their diagnosis and treatment.

Expression and significance of MMP-9 and MDM2 in the oncogenesis of lung cancer in rats

Objective:To observe the expression of matrix metalloproteinase-9(MMP-9)and mouse double minute 2 homolog(MDM2)in the oncogenesis of lung cancer in rats and to explore their clinical value.Methods:A total of 140 rats were selected,of which 20 were selected randomly as the control group;and the remaining 120 as the observation group.The observation group was injected with benzopyrene to establish diseases model such as tissue proliferation,abnormal proliferation and lung cancer.Delected the MMP-9 levels of lung tissue by enzyme-linked assay,detected the MDM2 levels of lung tissue by immunochemistry assay.Results:The MMP-9 and MDM2 expression of the lung cancer group and the abnormal proliferation group were significantly higher than that in the tissue proliferation group and the control group,the difference was significant(P<0.05).And the MDM2 expression of the tissue proliferation group was significantly higher than that in the control group,the difference was significant(P<0.05).There was no significant difference in the MMP-9 expression between the tissue proliferation group and the control group(P>0.05).The MDM2 and MMP-9 expression were increased in turn in the small cell carcinoma,squamous cell carcinoma and adenocarcinoma,the difference was statistically significant(P<0.05).The MMP-9 and MDM2 expressions of stageⅢand stageⅣlung cancer tissue in rats were significant higher than that during stageⅠand stageⅡ,the difference was significant(P<0.05).There was no significantly different in the MMP-9 and MDM2 expressions between stageⅢand stageⅣ(P>0.05),and there is no significant difference of the MMP-9and MDM2 expressions between stageⅠand stageⅡ(P>0.05).Conclusions:The expression of MMP-9 and MDM2 in lung tissue was associated with lung disease and lung cancer,both of them may be involved in the development and metastasis of lung cancer.Combined detection can be used as therapy and prognostic indicators for lung cancer.

Effects of Insulin-like Growth Factor 1 Receptor and Its Inhibitor AG1024 on the Progress of Lung Cancer

Summary： The type 1 insulin-like growth factor receptor （IGF-1R） and its downstream signaling com- ponents have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer （NSCLC）. This study aimed to investigate the effects of IGF-1R and its in- hibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues （n=198）. Western blotting was used to determine the expressions oflGF-1 and phosphorylated IGF-1R （p-IGF-1R） in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction （FQ-PCR）, respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1 ＋AG 1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-l＋AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF- 1 and IGF inhibitor AG 1024 promotes lung cancer progression.

Management of tyrosine kinase inhibitor resistance in lung cancer with EGFR mutation

The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by the universal development of resistance. Treatment failure can result from inadequate drug exposure or selection of resistant malignant clones. Clinically distinct mechanisms of disease progression have been identified and can inform treatment decisions. Investigations into the biochemical mechanisms of tyrosine kinase inhibitor resistance may provide additional therapeutic targets by which the efficacy of targeted therapy can be improved.

Epidemiological Evolution of Lung Cancer in the South of Spain from 1990 to 2010

Background: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes.Methods: Descriptive analysis of cases diagnosed with lung cancer in Hospital Virgen de las Nieves(Spain) from 1990 to 2010,based on five variables(age, sex, smoking, histology and pathological anatomy). The study establishes associations between these variables and compares the results with the literature.Results: 2,026 patients were diagnosed with lung cancer in this period; 1,838 were males(90.7%) and 188 women(9.3%); 1,892 patients(93.4%) were smokers or ex-smokers and 134(6.6%) had never smoked; the most frequent non-small cell histology types were squamous cell carcinoma and adenocarcinoma and it was the most frequent neoplasia in women and were associated with a lower tobacco consumption.Conclusion: The large majority of lung cancer cases is associated with a history of smoking tobacco and there are histopathological differences according to gender and cumulative tobacco smoke load.

Gender Does Not Have a Potential Predictive Value for the Presence of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma

Background: Previous studies reported that non-small cell carcinoma patients characterized by female gender, never-smoking status and adenocarcinoma histology were more likely to harbor epidermal growth factor receptor (EGFR) mutations. However, some studies failed to find the relationship between EGFR mutation and gender. Methods: One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. Since the smoking rate is significantly higher in men, we assumed that gender difference might be a seeming factor affected by smoking. Therefore we subdivided the patients into 2 groups: never- and ever-smokers. Results: The number of ever-smokers was 94.44% in men, whereas 8.51% in women. EGFR mutation was positive in 48.9%. For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure/mixed groundglass opacity (GGO) on computed tomography (CT) and smoking status. However, in ever-smokers, EGFR mutation status was associated with lepidic histologic subtype and GGO on CT, but not others including gender. Similar results were also found in never-smokers, and gender was not also related to EGFR mutation in never smokers. Conclusion: The EGFR mutational frequency among men and women was not significantly different when lung adenocarcinoma patients were stratified into never- and ever-smokers.

The role of stem cells in airway repair:implications for the origins of lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.

Polymorphisms of GSTs in Lung Adenocarcinoma Patients Followed in the Context of a Biobank

Background: Lung Adenocarcinoma (ADC) has been recently associated with distinct molecular changes, leading to the development of molecular-based targeted therapy. The Nancy’s Centre of Biological Resources (“Centre des Ressources Biologiques”, CRB) is an ISO 9001-2000 certified biobank with biological material and follow-up data from lung cancer patients, which collected during the last 20 years. Objective: To estimate and compare the frequency of Glutathionne S-Transferase (GST) polymorphisms in a French population of ADC patients. Methods: A retrospective study was conducted by the CRB between 1988 and 2007: 296 consecutive patients operated upon for ADC and 447 healthy subjects were evaluated. Genomic DNA was obtained from peripheral blood samples collected in EDTA tubes. The DNA was extracted using proteinase K digestion and phenol: chloroform purification. The GST polymorphisms were studied with duplex SYBR Green q PCR using specific primers and results being read on melt curves. Results: Two GST classes were monitored during this research. The Mu class GST (GSTM) and the Theta class GST (GSTT) members. We studied the incidence of each genotype, as well as the GSTMT (combined Mu and Theta class) and null genotype in ADC and control patients. ADC patients had a higher incidence of the GSTM polymorphism (p 0.0001, 95%CI 1.63 - 3.24) and a lower incidence of the GSTT polymorphism (p 0.0001, 95%CI 0.31 - 0.66) comparing to control. The null and GSTMT genotype had no significant statistical differences between the two groups. Conclusion: ADC patients were found to have a higher incidence of the GSTM genotype and a lower incidence of the GSTT genotype, compared to controls. Future studies may help elucidate the possible contribution of these genotypic differences in lung adenocarcinoma carcinogenesis or regarding the response to chemotherapy.

Gingival Metastasis Revealing Lung Adenocarcinoma

Introduction:?The lung adenocarcinoma is an invasive malignant tumor. Its visceral metastases are multiple. The gingival location is uncommon if not exceptional. Observation: We report the case of 66-year-old patient with a right cervical radiculopathology. Clinical examination objectified a superior vena cava syndrome with gingival tumor budding whose excisional biopsy found a location of a poorly differentiated and infiltrating carcinoma. The bronchoscopy revealed a tumor nodule obstructing the right mainstem bronchus with the histological study concluded as a moderately differentiated adenocarcinoma infiltrating. Conclusion: Gingival metastasis revealing lung adenocarcinoma is uncommon even exceptional. It may delay the diagnosis and management of already poor prognosis.

Metachronous, Ipsilateral Primary Lung Cancer: A Case Report

Lung cancer is the most common malignant tumor in men worldwide. It has been documented that patients can develop multiple primary lung cancer, with a 5% annual risk of a second primary (metachronous) cancer occurring after prior curative treatment. Moreover, there has been an increase in the incidence of metachronous primary lung cancer reflecting a longer survival after curative resection of the primary cancer and improvements in patient surveillance methods. Herein, we present a case of a patient diagnosed with a metachronous primary lung cancer presenting 1 year after treatment of a primary lung cancer at National Chest Hospital, Kingston, Jamaica. Through strict adherence to surveillance guidelines, this metachronous cancer was detected, enabling the patient to be promptly treated.

Clinical Significance of a Rise in AFP in Lung Adenocarcinoma Patients with Liver Metastasis:One Case Report and Literatures Review

IntroductionUsually the alpha fetoprotein （AFP） concentration of patients with metastatic liver cancer is slightly raised. Most of the levels are lower than 400 ug/L. Following biopsies of lung and liver neoplasms, one patient with a clinical diagnosis of lung cancer plus liver metastasis was pathologically diagnosed having an adenocarcinoma. His serum AFP value was 100-300 times the normal value. In order to further explore the clinical significance of an elevation of the AFP level in patients with lung adenocarcinoma plus liver metastasis, and to precisely distinguish a simple liver metastasis from lung adenocarcinoma or from lung hepatoid adenocarcinoma （HAC）, a clinical analysis of the patient, and a literature review was conducted.

Pre-malignant processes of smoking-induced lung adenocarcinoma development: A conceptual biological model

Chronic exposure to cigarette smoke is the leading cause of human lung cancer and its most prevalent form, adenocarcinoma. However, the mechanisms by which smoking induces adenocarcinoma are largely inferred from the analysis of fully developed tumors. The current work focuses on the early events that precede the existence of clinically detectable tumors and where the progressive mechanisms are believed to be different from the ones driving established tumor growth. Biological information was drawn from the literature and generalized into a conceptual model, or framework, which describes and integrates the main processes involved in the early stages of smoking-induced lung adenocarcinoma development. No such integrative representation currently exists. The biological framework presented here is based on the “field of injury” of the lung. It covers the smoking-induced stepwise transition of unexposed (naive) lung tissue to the first appearance of neoplastic cells through defined tissue states referred to as pre-field and field. Each tissue state exhibits its own formalized characteristics (or phenotype properties), which evolve as a result of the combined effects of smoking, the interactions between the different tissue properties, and the local environment represented in the framework as lung inflammation and immune surveillance. The resulting network of influences between the lung tissue states and properties provides a good understanding of the early events involved in lung adenocarcinoma triggered by smoking. The resulting conceptual model—an integrative mechanistic hypothesis—can explain a broad range of cigarette smoking and smoking cessation scenarios.

EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma

Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.

ABCA3作为非小细胞肺癌的预后生物标志物及其与免疫细胞浸润的相关性

目的 本研究旨在基于生物信息学分析探讨ABCA3在非小细胞肺癌——肺腺癌(lung adenocarcinoma,LUAD)中的临床意义和生物学功能。方法 基于癌症基因组图谱(the Cancer Genome Atlas,TCGA),提取LUAD中ABCA3表达和相应的临床信息。使用R4.2.2软件进行统计分析。采用Wilcoxon符号秩和检验比较TCGA LUAD队列中肿瘤组织与对照组之间ABCA3的表达,以及临床病理参数与ABCA3表达水平之间的关系。根据ABCA3表达的中位数,将TCGA LUAD患者分为高表达组和低表达组。使用survival包和survminer包分析ABCA3与LUAD患者总生存(overall survival,OS)期和无进展生存(progression free survival,PFS)期的关系,并进行单因素和多因素Cox回归分析确定与LUAD预后相关的危险因素。使用rms包构建预测LUAD患者1年、2年和3年OS率的列线图模型。使用DESeq2包对高表达组和低表达组患者进行差异表达基因(differential expressed genes,DEGs)分析,并使用cluster Profil er包对DEGs进行基因本体(Gene Ontology,GO)数据库和基因组京都百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。利用CIBERSORT算法预测LUAD肿瘤样本和正常样本中22种浸润性免疫细胞的丰度,并分析ABCA3表达与免疫浸润细胞和免疫检查点之间的相关性。结果 ABCA3基因在LUAD肿瘤组织中的表达均低于配对和非配对样本正常组织(P<0.05)。ABCA3高表达LUAD患者的OS (P=0.031)和PFS (P=0.044)明显高于低表达患者。T2分期(P=0.004)和T3分期(P=0.044)患者ABCA3的表达显著低于T1分期患者。多因素Cox回归分析显示,T分期、N分期和ABCA3表达是影响LUAD预后的独立影响因素(P<0.05)。基于ABCA3表达、T分期和N分期构建的列线图预测模型的C-index为0.86,提示模型与实际结果较为一致。校准曲线中的偏差修正线接近理想曲线,提示列线图模型的预测结果与观测结果较吻合。基因集富集分析显示ABCA3高表达组主要与花生四烯酸代谢、补体和凝血级联、肠道免疫网络免疫球蛋白A产生等有关。ABCA3的表达与NRP1、TRFRSF14、TNFSF15、CD40LG、HHLA2、CD28呈明显正相关,而与IDO1、CD70、TNFSF4、CD276和VTCN1呈明显负相关(P<0.05)。12种免疫浸润细胞在高表达组和低表达组存在明显差异(P<0.05)。此外,14种免疫浸润细胞与ABCA3表达呈现明显相关性(P<0.05),包括巨噬细胞、CD4+T细胞和树突细胞。结论 ABCA3的表达与LUAD患者预后和免疫细胞浸润有关,可能是预测非小细胞肺癌预后的有价值生物标志物。

基于失巢凋亡相关基因预测肺腺癌转移及预后模型的构建与验证

目的:失巢凋亡是一种特殊的程序性细胞死亡,在肿瘤转移中发挥重要的作用。肺腺癌常发生多器官扩散性转移,严重影响患者的预后。本研究旨在探索新的失巢凋亡相关标志物预测肺腺癌转移及预后。方法:从TCGA数据库和GEO数据库获取肺腺癌转移患者和未转移患者的基因表达谱和相应的临床数据,从GeneCard数据库下载293个失巢凋亡相关基因。通过无监督聚类分析,将肺腺癌转移患者分成两组肿瘤亚型,TIMER数据库和单样本基因集富集分析评估两组的免疫浸润和免疫细胞功能。接着,采用最小绝对收缩和选择算法和Cox回归模型构建失巢凋亡相关基因预后模型并进行外部数据集验证,ROC曲线和列线图进一步评估模型的预测能力。同时,评估了高风险组和低风险组的免疫治疗和药物治疗差异。最后,通过实时荧光定量PCR (qRTPCR)验证标记基因的表达以及多重免疫荧光组化验证标记基因的免疫细胞浸润。结果:两聚类分子亚型在临床病理特征、预后和免疫细胞浸润方面存在显著差异。Lasso及多因素Cox回归筛选得到了3个失巢凋亡相关预后基因(TLE1、EIF2AK3和BIRC3),构建3基因风险模型。根据风险评分中位值将患者分为高、低风险组,低风险组表现出更高的总生存期时间,免疫活性,肿瘤突变负担和PD1/PDL1表达,这与免疫检查点抑制剂的更好应答一致。列线图一步证明了模型的优越预测价值。qRTPCR显示,3个预后标志基因在肺腺癌细胞系和肺腺癌组织表达更高,多重免疫荧光组化验证其表达与免疫细胞浸润程度正相关。结论:综上所述,本研究建立了失巢凋亡相关基因为特征的预后风险模型,该模型在肺腺癌患者中有很好的预后预测价值,因而可作为评估肺腺癌患者预后的潜在诊断标志物和治疗靶点。

液基细胞学联合免疫细胞化学对肺腺癌胸腔积液的诊断价值

目的研究液基细胞学联合免疫细胞化学染色对肺腺癌胸腔积液的诊断价值。方法收集中山大学附属第三医院病理科2022年6月至2023年2月送检的50例胸腔积液样本,以细胞蜡块免疫组化作为诊断标准,其中30例确诊为肺腺癌,20例为非腺癌积液(包括17例非肿瘤积液、2例小细胞肺癌和1例肺鳞癌),均采用液基薄层制片技术中的沉降式液基薄层细胞制片技术(liquid-based cytology technology,LCT)和膜式薄层细胞制作技术(thinprep cytologic test,TCT)制片,行免疫细胞化学染色,比较分析液基细胞学免疫细胞化学染色的可行性。结果液基细胞学联合免疫细胞化学诊断结果与细胞蜡块免疫组织化学诊断结果一致,但TCT制片法明显优于LCT制片法,样本间细胞数量一致,分布均匀,阳性染色定位准确,细胞质和细胞核呈色清晰。TTF-1、napsin A、CK7在TCT联合免疫细胞化学检测肺腺癌的灵敏度分别100%、91.66%、93.10%,特异性为100%、100%、83.33%;而P40在1例肺鳞癌中弥漫表达。结论液基细胞学联合免疫细胞化学在胸腔积液肺腺癌的诊断中表现出较高的敏感性和特异性,在临床工作尤其是晚期患者原发灶难以获取的患者具有重要价值;因其操作时间短,在缩短报告时长方面更显示出巨大优势。

补虚活血镇痛方内服联合中药外敷治疗晚期肺腺癌癌痛的效果

目的探究补虚活血镇痛方内服联合中药外敷治疗晚期肺腺癌癌痛的效果。方法本研究为前瞻性随机对照试验,选择104例晚期肺腺癌癌痛患者,按照随机数字表法分为对照组和观察组,各52例。对照组给予常规西医治疗,观察组在对照组基础上加用补虚活血镇痛方内服联合中药外敷,7 d为1个疗程,2组均治疗2个疗程。评价指标包括中医症候积分、疼痛程度、疼痛介质和不良反应发生情况。结果观察组与对照组研究期间各剔除2例,最终观察组和对照组各50例完成研究。治疗2个疗程时,2组各项中医症候积分均显著下降,且观察组各项中医症候积分低于对照组,差异有统计学意义(P<0.05)。治疗1个疗程和2个疗程时,2组视觉模拟评分法(VAS)评分均显著下降,且观察组低于对照组,差异有统计学意义(P<0.05);治疗2个疗程时,2组5-羟色胺(5-HT)、前列腺素E2(PGE2)和内皮素-1(ET-1)水平均显著下降,且观察组低于对照组,差异有统计学意义(P<0.05)。2组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论补虚活血镇痛方内服联合中药外敷可有效改善晚期肺腺癌癌痛患者症状,减轻疼痛程度且下调疼痛介质水平,用药安全性良好。

百里醌通过诱导铁死亡调控人肺腺癌A549/DDP细胞顺铂的耐药性

目的:研究百里醌对A549/DDP(人肺腺癌顺铂耐药细胞)细胞顺铂耐药性的影响,并探讨其作用机制。方法:不同浓度百里醌或者顺铂处理A549/DDP细胞,采用CCK8和平板克隆实验检测细胞增殖能力;流式细胞术检测细胞凋亡;流式细胞术检测不同分组中细胞ROS水平;Western blot检测SLC7A11、GPX4、ACSL4等铁死亡相关蛋白的表达。结果:百里醌对A549/DDP细胞的增殖具有抑制作用,并呈剂量和时间依赖性。顺铂联合百里醌与单纯应用顺铂组相比,A549/DDP细胞增殖能力减弱,凋亡率升高。此外,与顺铂单独处理组相比,顺铂联合使用百里醌后,细胞中ROS水平明显升高,ACSL4水平升高,SLC7A11和GPX4蛋白水平明显降低。在加入铁死亡抑制剂Ferrostatin-1后可逆转A549/DDP细胞中ROS水平以及ACSL4、SLC7A11和GPX4等相关蛋白的变化,差异具有统计学意义。结论:百里醌通过诱导铁死亡调控人肺腺癌A549/DDP细胞顺铂的耐药性。