Expression of nm23-H1 and nm23-H2 protein in endometrial carcinoma.

nm23 gene expression has been shown to be inversely correlated with tumour metastatic potential in some cancers but not in others. Examination was made of the expression of nm23-H1 and nm23-H2 gene products by immunohistochemistry and immunoblotting in 28 endometrial carcinomas. Immunohistochemistry indicated the cytoplasm of cancer cells to be positive, and myometrium and endometrial stromal cells negative, for nm23-H1 and -H2 protein. The staining intensity for these proteins was significantly stronger in well-differentiated adenocarcinomas (G1) than in those moderately differentiated (G2) (P < 0.05). nm23-H1 and -H2 proteins were shown by immunoblotting to be present at significantly higher levels in G1 than in G2 tumours (P < 0.05). Two of eight cases expressed high nm23-H1 and -H2 protein in poorly differentiated adenocarcinomas (G3). In G3 tumours, nm23 expression may be diverse. In this study, the expression of nm23-H1 and -H2 was not correlated with stage, metastasis, tumour size, myometrial invasion, oestrogen receptor, progesterone receptor or menopause. It follows from the findings presented above that the high expression of nm23-H1 and -H2 is positively correlated with histological differentiation.     

Expression of nm23 protein in adult soft tissue sarcoma is correlated with histological grade

BACKGROUND: There is controversy about whether expression of nm23 is involved in suppression of metastases or contributes to tumour progression. Few studies have examined the role of nm23 in sarcomas. The aim of this study was to determine if expression of nm23 protein or its H1-subtype correlated with clinicopathological parameters in adult soft tissue sarcomas (STS). MATERIALS AND METHODS: Protein expression was examined by immunohistochemistry on paraffin-embedded sections of 46 STS patients, quantified using a colour video imaging system and correlated to histological grade. The monoclonal antibodies used were anti-nm23 (recognising both nm23-H1 and nm23-H2) and anti-nm23-H1 (recognising nm23-H1 only). RESULTS: High-grade tumours significantly overexpressed nm23 (including both nm23-H1 and nm23-H2) compared with both intermediate and low-grade tumours (ANOVA and Tukey, all p < 0.05). Multiple regression analysis confirmed the significance of the relationship and independence of the nm23 (p = 0.005), but not nm23-H1. CONCLUSION: Expression of nm23 protein, particularly nm23-H2, is an independent predictor of malignant potential of adult STS.     

CD44V6、E-cadherin和nm23-H1在肾细胞癌中的表达及意义

目的　探讨CD44V 6、E cadherinhe和nm 2 3 H 1蛋白表达与肾细胞癌 (RCC)的发生、发展及转移的关系。方法　采用免疫组化SP方法 ,检测 46例肾细胞癌组织和 10例正常肾组织中CD44V 6、E cadherin和nm 2 3 H 1蛋白的表达情况。结果　CD 44V 6蛋白在肾细胞癌组织中的阳性表达率为 2 6.1% ,CD 44V 6高表达与肾细胞癌脉管浸润转移呈正相关 (P <0 .0 5 )。nm 2 3 H 1和E cadherin蛋白在肾细胞癌组织中阳性表达率分别为 2 3 .9%和 5 8.7% ,显著低于正常肾组织 ( 10 0 .0 % ) (P <0 .0 1)。nm 2 3 H 1和E cadherin阳性表达与肾细胞癌的组织学分级相关 (P <0 .0 5 )。CD 44V 6、E cadherin、nm 2 3 H 1阳性表达与肾细胞癌组织学分型和肿瘤大小无关 (P >0 .0 5 )。结论　CD44V 6蛋白高表达和E cadherin、nm 2 3 H 1蛋白低表达是判断肾细胞癌的生物学行为的良好指标。     

Nm23-H1 expression does not predict clinical survival in colorectal cancer patients

The gene Nm23, which encodes for a nucleoside diphosphate kinase, has been defined as a metastasis-suppressor gene because of the inverse correlation between its expression and the metastatic capacity of the tumor cells. For colorectal cancer, however, the findings are equivocal. The aim of our study was to assess, in 160 patients undergoing surgery for colorectal cancer (CRC), the expression of the Nm23-H1 protein and to evaluate its possible associations with traditional clinicopathologic variables, with DNA-ploidy and proliferative activity (S-phase fraction, SPF), and with disease-free and overall survival of patients. Nm23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry; DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. The median follow-up time in our study group was 71 months (range 34-115 months). No association was observed between Nm23-H1 protein expression and clinicopathological variables, S-phase fraction and DNA-ploidy. Furthermore, no significant differences were observed in the survival of patients with either moderate or strong Nm23-H1 expression. The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA aneuploid tumors and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. Our results indicate that Nm23-H1 activity is tissue-specific and that in CRCs the expression of the protein is not associated with tumor progression and patient prognosis, although further studies are required in order to throw more light on the possible clinical significance of the overexpression of the protein Nm23-H1 in such tumors.     

The role of nm23-H1 in the progression of transitional cell bladder cancer.

The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23-H1 as a metastasis suppressor or prognostic indicator for human cancers remains enigmatic. Given that gene expression is regulated at the tissue-specific level, we studied the molecular mechanisms of nm23-H1 expression in human bladder cancer cell lines and the clinical importance of protein product (NM23-H1) in association with patient outcome (n = 257) by immunohistochemistry. We demonstrated that nm23-H1 is expressed in bladder cancer cells without genomic alterations. High NM23-H1 expression was found in 39 cases (15.2%), intermediate expression in 119 cases (46.3%), and low NM23-H1 in 99 cases (38.5%). NM23-H1 was inversely related to staging classification or tumor size (P < 0.05), with the most significant difference being observed between pTa tumors and those of pT1-pT3 bladder cancer (P = 0.01). Reduced NM23-H1, defined as intermediate and low levels of expression, tended to have a higher risk of tumor metastasis (P = 0.06) or poor longtime survival (P = 0.07). In the subset of grade 2 bladder tumors, reduced NM23-H1 significantly correlated with the occurrence of tumor metastasis or poor patient survival (P < 0.05). These findings overall suggest that nm23-H1 may play an important role in suppressing the early step of carcinogenesis and thus act as an invasion suppressor for human bladder cancer. A prospective study is required to clarify the potential of the molecular marker in prediction of disease progression.     

Expression of nm23-Hl and nm23-H2 Proteins in Prostate Carcinoma

The nm 23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm 23-H1 and nm 23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm 23-H1 or nm 23-H2 protein, respectively. Negative staining for nm 23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm 23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm 23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm 23-H2 protein was detected in 83% of primary tumors and its expression appeared to he significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm 23-H1 and nm 23-H2 expression. These data suggest that the nm 23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.     

Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma.

The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed > or = 20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment.     

nm23—H1基因在大肠癌中的表达与肝转移及预后的关系

目的：探讨ｎｍ２３－Ｈ１蛋白表达与大肠癌肝转移及预后的关系。方法：对１０１例大肠癌存档石蜡块进行重新切片，采用ｎｍ２３－Ｈ１单克隆抗体进行免疫组化染色（ＬＳＡＢ法）。结果：ｎｍ２３－Ｈ１蛋白表达与年龄、性别、肿瘤大小、部位、组织类型、浆膜侵犯无关；与Ｄｕｋｅｓ分期、淋巴结转移有关；手术时有肝转移组较无肝转移组低，手术后有肝转移复发组较无肝转移复发组低（Ｐ＜００１）。Ｃｏｘ模型分析显示ｎｍ２３－Ｈ１是大肠癌预后的一个保护性指标。结论：ｎｍ２３－Ｈ１基因对大肠癌肝转移和预后具有重要作用。ＬＳＡＢ法检测大肠癌组织中ｎｍ２３－Ｈ１蛋白表达可能是预测大肠癌肝转移及预后的生物学指标之     

幕上星形细胞瘤PCNA和nm23-H1表达与相关预后因素分析

目的　探讨星形细胞瘤PCNA、nm2 3 H1表达与患者的临床特征和MRI征象之间的关系 ,通过多因素分析筛选出影响星形细胞瘤患者预后的重要因素以指导临床治疗。方法　对随诊资料完整和病理诊断明确的术前行MRI平扫及增强检查、术后行放射治疗的 5 2例幕上星形细胞瘤患者的手术切除标本 ,采用SP免疫组织化学法检测其组织切片中PCNA及nm2 3 H1表达 ,结合患者的临床资料 ,进行相关分析和多因素分析。结果　星形细胞瘤PCNA表达水平在不同病理级别中差异有显著性意义 (P <0 .0 5 ) ,肿瘤组织的PCNA表达与瘤旁组织的表达差异有显著性意义 (P <0 .0 5 )。PCNA表达与星形细胞瘤患者生存率呈负相关 ,且PCNA表达与星形细胞瘤MRI征象中增强程度、最大横截面直径、信号不均匀性及瘤周水肿均明显相关 (P <0 .0 5 )。不同病理级别星形细胞瘤中 ,nm2 3 H1表达差异无显著性意义 (P >0 .0 5 ) ,但与瘤周正常组织的表达有差异。PCNA表达与nm2 3 H1表达无显著相关性 (P >0 .0 5 )。多因素分析显示影响星形细胞瘤患者生存率的主要因素有病理分级和PCNA表达水平。结论　PCNA表达水平可反映星形细胞瘤患者的预后情况 ,可间接推断瘤体的生物学特征和影像学表现 ,PCNA表达与病理分级结合 ,可作为有价值的监测指标。     

Reappraisal of the role of NM23-H1 in colorectal cancers

BACKGROUND AND OBJECTIVES: A number of evidence indicate that downregulation of the nm23-H1 gene may be relevant to metastatic progression of many kinds of human cancer. However, its role in colorectal cancers remains controversial. To address the issue, this study was performed to investigate the clinical relevance of nm23-H1 in patients with colorectal cancers. METHODS: Immunohistochemical expression of nm23-H1 protein product (NM23-H1) was studied in a total of 146 colorectal cancer patients and compared for its prognostic value at a mean follow-up of 54 months. RESULTS: There was no apparent correlation between NM23-H1 expression and clinicopathological indicators, including Dukes category, lymphatic metastasis, distant metastasis, histological grading, and tumor location (P < 0.1, respectively). In addition, determination of NM23-H1 expression status did not provide independent prognostic information compared with conventional pathological staging. CONCLUSIONS: The results indicate that nm23-H1 gene does not play an important part in the progression of colorectal carcinogenesis.     

MTA1和nm23-H1蛋白表达与乳腺癌生物学行为之间的关系

目的探讨肿瘤转移相关基因（NTA1）和nm23-H1蛋白表达与乳腺癌生物学行为之间的关系。方法运用免疫组化S-P法检测56例乳腺癌组织中NTAl、nm23-H1蛋白的表达。结果56例乳腺癌组织中39例NTA1蛋白阳性表达,阳性率为69．6％,NTA1高表达与乳腺癌组织学分级、临床分期和淋巴结转移关系密切（P〈0．05）;3l例nm23-H1蛋白阳性表达,阳性率为55．4％,nm23-H1低表达与乳腺癌组织学分级、临床分期和淋巴结转移关系密切（P〈0．05）;乳腺癌组织中NTA1、nm23-H1蛋白表达呈负相关（P〈0．05）。结论NTA1和nm23-H1蛋白表达与乳腺癌分化程度、淋巴结转移和预后关系密切,可作为诊断乳腺癌患者转移复发的参考指标,并有望成为乳腺癌基因治疗的新靶点。     

结直肠癌中CD44v6、MMP-2、nm23-H1表达与临床病理的相关性研究

 目的 探讨结直肠癌中ＣＤ４４ｖ６、ＭＭＰ－２和ｎｍ２３－Ｈ１的表达与临床病理特征的关系。方法采用免疫组化 ＳＡＢＣ法结合计算机图像分析技术检测 ＣＤ４４ｖ６、ＭＭＰ－２、ｎｍ２３－Ｈ１蛋白在 ２４例结直肠癌患者癌及癌旁组织中的表达。结果 ２４例结直肠癌组织中 ＣＤ４４ｖ６、ＭＭＰ－２的阳性单位（ＰＵ值）高于癌旁和正常组织（Ｐ＜０．０５），而 ｎｍ２３－Ｈ１的 ＰＵ值则低于癌旁和正常组织（Ｐ＜０．０５）。它们的异常表达与患者的性别、年龄、肿瘤大小及部位无相关性，而与浸润深度、淋巴结转移、远处转移、Ｄｕｋｅ’ｓ分期密切相关（Ｐ＜０．０５）。结论 ＣＤ４４ｖ６、ＭＭＰ－２、ｎｍ２３－Ｈ１与结直肠癌的病理特征密切相关。它们的异常表达在肿瘤的侵袭转移中可能具有正、负协同作用，联合检测 ＣＤ４４ｖ６、ＭＭＰ－２、ｎｍ２３－Ｈ１蛋白可作为预测结直肠癌侵袭转移及客观评价患者预后的生物学指标。     

食管鳞状细胞癌中nm23-H1和p53蛋白表达及其相互关系

目的:探讨食管鳞癌组织中p53和nm23-H1蛋白的表达与癌组织分化浸润转移的关系,以及探讨两者之间的相关性,并进一步分析癌组织中p53和nm23-H1蛋白表达对食管癌患者的预后意义。方法:采用免疫组织化学(S-P法)方法对100例人食管鳞癌组织中的p53和nm23-H1蛋白的表达情况进行检测。结果:100例食管鳞癌组织中,nm23-H1阳性表达者70例(阳性率为70%),p53阳性表达者64例(阳性率为64%)。nm23-H1蛋白表达与食管癌淋巴结转移有关(P<0.025),与食管鳞状细胞癌的分化程度、肿瘤部位、浸润深度、病变长度以及患者性别、年龄无关(P>0.05)。p53蛋白表达与食管鳞状细胞癌的分化程度、浸润深度有关(P<0.05),与食管癌淋巴结转移、肿瘤部位、病变长度、患者性别、年龄无关(P>0.05)。高分化鳞癌组织中p53明显低表达(29.2%);低分化鳞状细胞癌组织中p53表达明显增高(71.4%)。食管外膜受累者p53表达较高(56%);仅发生食管粘膜和(或)粘膜下浸润组的癌组织中未发现有p53蛋白的表达。食管癌组织中nm23-H1蛋白低(高)表达与p53高(低)表达之间有明显相关性(P<0.01)。nm23-H1和p53蛋白表达亦与食管癌的TNM分期密切相关(P<0.05)。食管癌TNM分期越晚,其癌组织中nm23-H1蛋白表达越低,p53蛋白表达越高。结论:nm23-H1基因低表达与p53基因高表达可能在食管鳞状细胞癌浸润转移过程中发挥重要作用。nm23-H1可以作为食管鳞状细胞癌患者预后的基因标记,其蛋白表达产物的检测可以用于患者预后的判断,并为患者治疗方案的制定提供参考。     

The intratumoral microvessel density and expression of bFGF and nm23-Hl in colorectal cancer

It has previously been reported that intratumoral microvessel density (IMD), and the expression of bFGF and nm23-H1 are useful prognostic markers in colorectal cancer (CRC). In this study, a total of 100 CRCs were evaluated histopathologically, and IMD, bFGF and nm23-H1 expression were assessed by immunohistochemistry. IMD of patients increased with grade and stage, and this increase was statistically significant (p<0.05). A significantly higher incidence of high bFGF expression scores was also associated with increasing grade and stage (p<0.05). However, there was no significant difference between the grades in nm23-H1 expression (p=0.234). nm23-H1 expression occurred with lower incidence in stages C1, C2 and D than in stages B1 and B2 (p<0.05). Thus, a negative correlation was found between nm23-H1 expression and stage or lymph node metastasis (LNM) (p<0.05). IMD and bFGF expression were positively correlated with grade, stage, LNM, and lymphovascular invasion. Although positive correlation was found between IMD and bFGF, nm23-H1 expression negatively correlated with both of them. As a result, in clinical practice, increased IMD and bFGF expression and decreased nm23-H1 expression may provide valuable information in characterizing the malignant phenotype.     

宫颈癌中nm23-H_1基因的不同表达与淋巴结转移及预后关系研究

目的　探讨nm2 3 -H1基因在宫颈癌组织中表达及其意义。方法　采用免疫组化法检测 88例宫颈癌组织中nm2 3 -H1基因表达 ;对nm2 3 -H1表达与临床病理因素及预后关系进行分析。结果　宫颈鳞癌与腺癌的表达阳性率分别为 46 4% (2 6 /5 6 )和5 6 2 % (18/32 ) ;在与临床病理指标的相关性分析中发现 :宫颈腺癌中 ,无淋巴结转移者nm2 3 -H1阳性率明显高于有淋巴结转移者(P <0 0 1) ;而鳞癌中nm2 3 -H1的表达与淋巴结转移无关 (P >0 0 5 )。另外 ,nm2 3 -H1的表达与宫颈癌的临床分期、病理分级、病灶大小无关。回顾性预后调查发现 ,nm2 3 -H1阳性患者的生存率明显高于阴性表达者 ,在鳞癌及腺癌中 ,P <0 0 5和P <0 0 1。结论　nm2 3 -H1表达与宫颈腺癌淋巴结转移呈负相关 ;与鳞癌淋巴结转移无关。nm2 3 -H1基因的表达可以作为宫颈癌预后的一项指标     

nm23－H1和CD44蛋白在鼻咽癌中的表达及其与临床的关系

目的：探讨鼻咽癌（ＮＰＣ）中ｎｍ２３－Ｈ１和ＣＤ４４的表达及其与临床的关系。方法：收集ＮＰＣ蜡块标本,应用免疫组化ＬＳＡＢ法,检测ｎｍ２３－Ｈ１和ＣＤ４４基因蛋白的表达,其中前者４８例,后者４０例,３７例同时进行了上述两种检测,将两种基因蛋白表达结果与其临床的关系进行研究分析。结果：ｎｍ２３－Ｈ１阳性表达率６０．４２％,其与颈淋巴结转移无关,但与转移之颈淋巴结大小有关;ｎｍ２３－Ｈ１的表达与放疗后     

结肠癌nm23-H1和CD44V6及PCNA表达与DNA含量及转移潜能的相关性

目的探讨 nm23-H1、CD44V6和PCNA和DNA含量在结肠癌生长、浸润、转移中的作用及其相互关系.方法采用免疫组化S-P方法检测 152例结肠癌nm23-H1、CD44V6和PCNA.同时采用流式细胞光度术测定60例结肠癌D NA含量.结果152例结肠癌nm23-H1阳性率与淋巴结转移,P<0. 05、癌组织分化关系密切,P<0.01;CD44V6表达与Dukes分期(P<0.05) 、肿瘤浸润深度(P<0.05)、癌组织分化(P<0.05)及淋巴结转移(P<0.01)密切相关;PCNA表达与Dukes分期及肿瘤浸润深度有关(P<0.05);nm23-H1和CD44 V6表达,两者呈负相关(P<0.01),CD44V6阳性nm23-H1阴性表达的患者淋巴结转移率高于CD44V6阴性nm23-H1阳性表达者(P<0.05).伴淋巴结转移的结肠癌CD44V6和PCNA共同阳性表达率和异倍体癌的发生率高于无转移组(P <0.05).异倍体癌CD44V6和PCNA过度表达,而nm23-H1低表达(P<0.05) .结论nm23-H1、CD44V6和PCNA及DNA含量在结肠癌中的表达与其发生发展、侵袭转移密切相关,尤其CD44V6和nm23-H1表达在结肠癌转移中起协调作用,可成为临床估计肿瘤转移潜能的重要参考指标.     

p53和nm23-H1蛋白表达与食管癌浸润转移的关系

Objective To study the relationship between expression of p53 and nm23-H1 and differentiation, invasiveness and metastasis in human esophageal carcinoma, and the correlation between expression of p53 and nm23-H1. Methods Expression of p53 and nm23-H1 in 50 patients with squamous cell carcinoma of esophagus was detected by using immuno-histochemical S-P methods. Results 35 cases (70%) and 32 cases (64%) of esophageal squamous cell carcinoma were positive for nm23-H1 protein and p53 protein, respectively. The expression of nm23-H1 was related to lymphatic metastasis (P<0.025), but not related to tumor differentiation, invasiveness, tumor location, tumor length, patient's gender and age (P>0.05). The lymphatic metastasis location positive group had a very lower expression of nm23-H1 and the negative rate was 70.8%, but the negative group had a higher expression and the positive rate was 65.4%. The expression of p53 was related to tumor differentiation and invasiveness (P<0.05), but not related to lymphatic metastasis, tumor location, tumor length, patient's gender and age(P>0.05). Among the three groups, the high differentiation group had the lowest expression of p53 and the positive rate was 29.2%, but the low differentiation group had the highest positive rate (71.4%). As for tumor invasiveness, the group of outer membrane of esophagus infiltrated had the highest p53 protein positive rate (56%), but in the group, of mucous or submucous layer infiltrated p53 protien was not detectable. The low expression of nm23-H1 and the high expression of p53 were also correlated. The expression of nm23-H1 and p53 were both correlated with TNM stage of esophageal carcinoma (P<0.05). The better esophageal carcinomas differentiated, the lower nm23-H1 expressed and higher p53 expressed. Conclusion Low expression of nm23-H1 and high expression of p53 play an important role in the progression of squamous cell carcinoma of esophagus. Nm23-H1 might beta gene markef in the prophecy of patients' prognosis and benefit tumor treatment clinically.     

nm23-H1小干扰RNA增强紫杉醇脂质体对肺腺癌细胞化疗的敏感性

目的 探讨抑制nm23-H1基因的表达后,紫杉醇脂质体对人肺腺癌A549细胞化疗敏感性的影响.方法 以人肺腺癌A549细胞为研究对象,将其分为nm23-H1-小干扰RNA(siRNA)转染组和未转染组.采用Western blot法检测两组A549细胞中nm23-H1蛋白的表达情况,采用四甲基偶氮唑蓝(MTT)法检测紫杉醇脂质体对两组A549细胞的生长抑制率,以流式细胞仪检测A549细胞的凋亡和细胞周期的变化.结果 转染nm23-H1-siRNA后,A549细胞中nm23-H1蛋白的表达水平明显降低.紫杉醇脂质体作用48 h后,A549细胞的生长抑制率随药物浓度的升高而升高,且转染组细胞的抑制率更高.当紫杉醇脂质体浓度≥5 μg/ml时,转染组的抑制效率明显高于未转染组(均P＜0.05).转染nm23-H1-siRNA后,A549细胞的凋亡率[(65.62±4.36)%]较未转染组明显增加[(43.78±5.56)%,P＜0.05],S期和G2/M期细胞所占的比例则有所下降[S期:分别为(15.73±3.21)%和(25.56±4.01)%,P＜0.05;G2/M期:分别为(31.91±3.12)%和(39.41±4.21)%,P＜0.05].结论 nm23-H1基因与紫杉醇脂质体的化疗抵抗有关,抑制nm23-H1基因的表达可以增强紫杉醇脂质体的化疗敏感性.

Abstract：

Objective To study the chemosensitivity of lung adenocarcinoma cell line A549 cells to liposome-encapsulated paclitaxel after treatment by nm23-H1-small interference RNA (nm23-H1-siRNA) in vitro. Methods The A549 cells were divided into two groups: non-transfected group and nm23-H1-siRNA-transfected group. Western blot analysis was used to detect the expression of nm23-H1. MTT and flow cytometry were used to determine the cell mortality rate, apoptosis rate and cell cycle after liposome-encapsulated paclitaxel treatment in both groups. Results The expression of nm23-H1 in A549 cells was significantly decreased after transfection with nm23-H1-siRNA. After treatment for 48 hours with liposome-encapsulated paclitaxel, the cell mortality rate was increased with the increasing concentration of liposome-encapsulated paclitaxel in both groups, but increased higher in the nm23-H1-siRNA-transfected group. When the concentration of liposome-encapsulated paclitaxel was above 5 μg/ml, the cell mortality rate was significantly higher than that in the non-transfected group (P<0.05). The proportion of apoptotic cells also increased in the nm23-H1-siRNA-transfected group, compared with that of the non-transfected group (t=3.812,P<0.05), while the proportion of cells at S and G2/M phase decreased after transfection with nm23-H1-siRNA (S phase:t=8.356,P<0.05;G2/M phase:t=7.256,P<0.05). Conclusions Nm23-H1 is related with the chemoresistance to liposome-encapsulated paclitaxel in lung adenocarcinoma cell line A549 cells. Inhibition of the expression of nm23-H1 by nm23-H1-siRNA can improve the in vitro chemosensitivity of A549 cells to liposome-encapsulated paclitaxel.