EXPERIMENTAL RESEARCH OF EFFECTIVENESS OF siRNA- Her-2/neu ON DRUG SENSITIVITY OF Her-2/neu-OVEREXPRESSING LUNG ADENOCARCINOMA CELL LINE

Lung cancer is a potentially systemic disease. Despite improvements in the detection and treatment of lung cancer in the past two decades, the overall 5-year survival remains <15%. Constitutive overexpression for Her-2/neu gene is a frequent event in a variety of human tumors, including non-small cell lung cancer (NSCLC), but not small cell lungcancer[1-5]. In recent years, many studies have explored the effects on chemosensitivity resulting from altered expression and activation of the Her…     

HYPERMETHYLATION OF p14^ARF PROMOTER REGION AND EXPRESION OF p14^ARF GENE PRODUCT IN NON-SMALL CELL LUNG CANCER

Objective： This study was designed to investigate promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer, and value the role of p14^ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods： Promoter methylation status and protein expression of p14^ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction （MSP）, restriction enzyme-related polymerase chain reaction （RE-PCR） and immunohistochemistry （IHC）. Results： The positive rates of p14^ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% （7/40） and 2.5% （1/40） respectively. There were statistically significant differences between them, P〈0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14^ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p〈0.01. Promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer showed significantly an inverse correlation （r=-0.56, P〈0.01）, and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion： Promoter methylation is a crucial mechanism of inactivation of p14^ARF gene. Promoter methylation of p14^ARF gene might he involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future.     

DYNAMIC PARAMETER OF MEMBRANE LIPID IN LUNG CANCER CELL LINES, CARCINOGENESIS CELLS AND CANCER CELLS ISOLATED FROM PATIENTS WITH LUNG CANCER

With the aid of the Fluorescent lipophilic probe DPH (1, 6- diphenyl- 1, 3, 5- hexatriene ), the degree of microviscosity (η) and lipid fluidity (LFU) obtained from lung cancer lines and carcinogenesis cells induced by irradiation as well as the patients with lung cancer were quantitatively monitored by Fluorescence polarization. The results have shown a marked decreased in η and a significant increase in LFU in various tumor cells as compared to normal cells. Sometime, the degree of fluidity in carcinogenesis cells Induced by radiation and the patients with lung cancer have shown to be similar pattern. The possibility that these dynamic parameter may serve as a diagnostic tool for an early detection of lung cancer is discussed.     

Determination of PDCD5 in peripheral blood serum of cancer patients

Objective:Programmed cell death 5 (PDCD5) is an apoptosis related gene and plays an important role in the pathogenesis and development of cancer.Whether PDCD5 is present in peripheral blood serum has not been reported.The aim of this study is to determine the contents of PDCD5 protein in peripheral blood serum of cancer patients,as well as normal subjects.Methods:ELISA was used to detect the serum PDCD5 concentrations in 100 normal persons,83 patients with breast cancer,74 patients with gastrointestinal tract cancer and 41 patients with lung cancer.The results were statistically analyzed and discussed.Results:PDCD5 could be detected in peripheral blood serum in both normal subjects and cancer patients.The serum PDCD5 contents in normal persons ranged from 3.8 to 6.1 ng/ml with a median of 4.70±0.68 ng/ml.For cancer patients the PDCD5 levels were 4.59±0.90,4.79±1.14 and 10.43±22.34 ng/ml for breast cancer,gastrointestinal cancer and lung cancer patients respectively.There was no statistically significant difference between the serum PDCD5 concentrations of normal persons and cancer patients.Conclusion:PDCD5 is present in peripheral blood.The PDCD5 levels in cancer patients are not statistically different from that of normal persons,though decreased expression of PDCD5 in malignant tissues has been found.     

FACTORS AFFECTING THE HEALTH-RELATED QUALITY OF LIFE IN LUNG CANCER PATIENTS: MEASURED BY EORTC QLQ-C30 QLQ-LC13

Lung cancer is the most common cancer for both men and women in the world, accounting for 1.2 million new cases annually[1]. It is a growing worldwide problem, especially in developing countries. The majority of patients with common lung cancer will not be cured by local or system therapy. Because the outlook for lung cancer remains gloomy in terms of prognosis and survival, with over 80% of patients died within a year of diagnosis, and treatment tends to be largely palliative[2,3], the purpos…     

CHEMOPREVENTION OF LUNG CANCER IN THE HIGH INCIDENCE AREA

Since 1984, mass screening for cancer and chemopreventive trials in the two high incidence areas of lung cancer have been carried out. Chemo preventive trials on the subjects having moderate or severe atypical hyperplasia cells in the sputum were done by treatment with R1 [N-(p-ethoxycarbophenyl) retinamide] and R2 [N-(p-carboxyphenyl) retina-mide]. Results showed that the general status of the patients had improved. IgA and IgM in the serum were increased and the arsenic skin lesions were relieved after the treatment with Rl and R2. The ratio of the incidence of lung cancer for the treated group and the control group was 1:4, and the mean degree of hyperplasia in the sputum had dropped. It is suggested that these drugs are both safe and effective in the chemoprevention of lung cancer.     

Relationship between ERCC2 Polymorphism and Risk of Lung Cancer in Chinese Nonsmoker

Objective: Excision repair cross-complimentary group 2 (ERCC2) is one of the important DNA repair genes. ERCC2 codon 751 polymorphism has been shown to modulate cancer risk. We therefore assessed the relationship between the ERCC2 polymorphism and the susceptibility to lung cancer in nonsmoking females via a hospital-based case-control study. Methods: There were 105 lung cancer cases and matched healthy controls in this study. Information concerning demographic and risk factors was obtained, each person donated 2 ml blood for biomarker testing. ERCC2 genotypes were determined by PCR-RFLP method. All of the statistical analyses were performed with SPSS (v 12.0). Results: All of the subjects in this study were nonsmoking females in Shenyang. There was significant difference between the frequencies of ERCC2 polymorphism in cancer cases and controls (P<0.05). The frequencies of ERCC2 751 Gln allele were 6.2% in controls and 13.8% in cancer cases. The individuals with Lys/Gln Gln/Gln combined genotype were at an increased risk for lung cancer as compared with those carrying the Lys/Lys genotype (adjusted OR=2.80, 95%=CI 1.21?6.48). We analyzed the environmental risk factors for lung cancer in nonsmoking females. The cancer patients showed a higher prevalence of exposure to cooking fumes compared with controls (OR=2.44, P<0.05). Furthermore, an interaction between exposure to cooking fumes and the variant ERCC2 751 Gln allele on the risk of lung cancer was observed. Individuals with both risk genotype and exposure to cooking fumes had a higher risk of cancer than those with only one of them. Conclusion: The above findings indicate that the genetic polymorphism in the ERCC2 codon 751 is associated with the risk of lung cancer in nonsmoking females.     

Progress in lung cancer treatment

Lung cancer is the most common cause of cancer-related death in China.In recent years,the achievements in the fight against lung cancer have been fruitful.In this column,we introduce the achievements in lung cancer treatment from four different aspects.Radiation therapy is one of the main treatments for lung cancer,and is increasingly playing a role in the treatment of lung cancer.In recent years,great progress     

中国四川北部肺癌患者谷胱苷肽硫转移酶M1基因多态性分析

Objective To analyze the genetic polymorphism of GSTM1 to lung cancer patients in north Sichuan of China and compare with race from other district.Methods PCR-based technique was used to detect the genotypes of GSTM1 in lung cancer patients.Results In local lung cancer patients,the frequency of homozygous deletions(null genotype) for GSTM1 was 58.4 % (73/125).Among the patients,the frequencys of null genotype for GSTM1 were 62.5 % (20/32) in female,56.9 % (53/93) in male,56.1% (32/57)in patients with squamous cell carcinoma and 54.8 % (17/31) in patients with adenocarcinoma,respectively.The frequency of deletions of GSTM1 in lung cancer patients from north Sichuan of China is slightly exceeding those of Europe and Americas (P ＜0.05) and similar to the domestic result (P ＞0.05).Conclusion The genetic polymorphism of GSTM1 to lung cancer patients in north Sichuan of China dosen' t show distinguished feature for this district and race.     

中国四川北部肺癌患者谷胱苷肽硫转移酶M1基因多态性分析

Objective To analyze the genetic polymorphism of GSTM1 to lung cancer patients in north Sichuan of China and compare with race from other district.Methods PCR-based technique was used to detect the genotypes of GSTM1 in lung cancer patients.Results In local lung cancer patients,the frequency of homozygous deletions(null genotype) for GSTM1 was 58.4 % (73/125).Among the patients,the frequencys of null genotype for GSTM1 were 62.5 % (20/32) in female,56.9 % (53/93) in male,56.1% (32/57)in patients with squamous cell carcinoma and 54.8 % (17/31) in patients with adenocarcinoma,respectively.The frequency of deletions of GSTM1 in lung cancer patients from north Sichuan of China is slightly exceeding those of Europe and Americas (P ＜0.05) and similar to the domestic result (P ＞0.05).Conclusion The genetic polymorphism of GSTM1 to lung cancer patients in north Sichuan of China dosen' t show distinguished feature for this district and race.     

Activity of dolastatin 10 against small-cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification

Purpose: Dolastatin 10 is a natural cytotoxic peptide which acts through the inhibition of microtubule assembly. Studies have suggested that such agents can induce apoptosis in association with bcl-2 phosphorylation. Since bcl-2 overexpression is common in small-cell lung cancer (SCLC), we evaluated the activity of dolastatin 10 in SCLC cell lines and xenografts. Methods: In vitro growth inhibition was evaluated with a standardized MTT assay and apoptosis with fluorescent microscopy and a TUNEL assay. Immunoblot analysis and phosphatase digestion were used to determine bcl-2 modification. In vivo activity was evaluated in subcutaneous and metastatic SCLC xenograft models in SCID mice. Results: Dolastatin 10 had growth inhibitory activity against four SCLC cell lines (NCI-H69, -H82, -H446, -H510) with IC₅₀ values ranging from 0.032 to 0.184 nM. All four cell lines exhibited evidence of apoptosis after 48 h of exposure to 1.3 nM dolastatin 10. Immunoblot analysis revealed that 1.3 nM dolastatin 10 altered the electrophoretic mobility of bcl-2 in NCI-H69 and -H510 cells within 16 h of treatment. Incubation of protein extract from dolastatin 10-treated NCI-H69 and -H510 cells with calcineurin resulted in the disappearance of the altered mobility species, suggesting dolastatin 10-induced bcl-2 phosphorylation. In in vivo studies, 450 μg/kg of dolastatin 10 IV × 2 given after intravenous injection of NCI-H446 cells completely inhibited tumor formation. In established subcutaneous NCI-H446 xenografts, 450 μg/kg of dolastatin 10 IV induced apoptosis in the majority of tumor cells within 96 h, resulting in a log₁₀ cell kill of 5.2 and an increase in median survival from 42 to 91 days. Conclusions: These findings suggest that dolastatin 10 has potent activity against SCLC and that the modulation of apoptotic pathways deserves further evaluation as an anticancer strategy. Received: 14 July 1998 / Accepted: 3 September 1998     

Activity of fenretinide plus chemotherapeutic agents in small-cell lung cancer cell lines

Purpose: Fenretinide [N-(4-hydroxyphenyl)retinamide, 4HPR], a synthetic retinoid, is a potent inducer of apoptosis in small-cell lung cancer (SCLC) cell lines that may act through the generation of reactive oxygen species, suggesting that it may enhance the activity of other cytotoxic agents. In light of 4HPR's clinical potential and potent activity against SCLC cells, we evaluated the in vitro activity of 4HPR in combination with cisplatin, etoposide or paclitaxel. Methods: The growth-inhibitory activities of single-agent 4HPR, cisplatin, etoposide or paclitaxel, and combinations of 4HPR and individual chemotherapeutic agents, were evaluated using an MTT assay in two SCLC cell lines. Each two-drug combination was studied over a range of concentrations at a fixed ratio corresponding to the ratio of the IC₅₀ values of the individual agents. Data were analyzed by median-effect analysis as previously applied to drug combination studies. Results: All four agents inhibited growth in a dose-dependent manner in the NCI-H82 and NCI-H446 SCLC cell lines. At clinically reported drug concentrations that resulted in over 50% growth inhibition, the activities of the combinations 4HPR and cisplatin and 4HPR and etoposide were more than additive in both cell lines, and the activity of 4HPR plus paclitaxel was more than additive in NCI-H446 cells. Conclusion: 4HPR's potent single-agent activity, minimal toxicity, and potential synergy with standard cytotoxic drugs will allow for the development of promising investigational regimens for the treatment of patients with SCLC. Received: 17 February 1998 / Accepted: 20 May 1998     

小细胞肺癌组织显著低表达的SPIDR通过降低血清依赖促进NCI-H446细胞增殖

目的：探讨同源重组修复途径关键调控蛋白SPIDR在小细胞肺癌（small cell lung cancer,SCLC)中的作用与机制。方法：收集2013 年1 月至2015 年1 月上海肺科医院进行肿瘤手术切除、气管镜穿刺的SCLC患者癌组织标本60 例及正常人群肺组织标本44 例,qRT-PCR检测临床组织样本SPIDR mRNA表达水平;经稳定过表达SPIDR 改变NCI-H446 细胞表达水平后,采用MTT、小鼠荷瘤实验等实验方法,在体内、体外探究SPIDR 表达水平对SCLC细胞增殖等影响。结果：吸烟与患者SCLC的发生显著有关（P<0.01）;SPIDR mRNA在SCLC 组织样本中的表达显著低于正常肺组织（P<0.01）。人肺胚成纤维细胞株MRC-5 中SPIDR mRNA和蛋白表达水平明显高于SCLC细胞株NCI-H446（均P<0.05）。在10%胎牛血清常规培养体系中,过表达SPIDR对NCI-H446 细胞增值和化疗药物敏感性无明显影响（均P>0.05）,但小鼠荷瘤实验从第9 天开始,过表达SPIDR组（pMSCV-SPIDR）的瘤体积与原始NCI-H446 组和空载体组（pMSCV）开始出现明显差异,第27 天pMSCV-SPIDR 组移植瘤平均体积分别比原始NCI-H446 组与空载体组缩小58.99%和61.84%（均P<0.01）。在含1%~3%胎牛血清的非常规培养体系中,过表达SPIDR 的NCI-H446 细胞增殖速度显著低于原始NCI-H446 组和空载体组（P<0.05 或P<0.01）。结论：SCLC组织中SPIDR表达水平明显低于正常肺组织,过表达SPIDR的NCI-H446 细胞体内及体外低血清含量培养（<3%）生长速度显著低于对照组,表明SPIDR以低血清浓度依赖方式影响SCLC细胞增殖。     

小细胞肺癌细胞系NCI-H446蛋白质表达谱的建立

背景与目的:小细胞肺癌(smallcelllungcancer,SCLC)是一种侵袭性极强的恶性肿瘤,具有增长迅速、早期转移等特点。目前公开的数据库中尚未见到小细胞肺癌的双向电泳参考图谱及其蛋白表达谱。本研究目的是建立高分辨率的小细胞肺癌细胞系NCI-H446细胞双向凝胶电泳图谱,并初步分析其蛋白质表达情况。方法:用固相pH梯度双向凝胶电泳技术(IPG-DALT)分离NCI-H446细胞总蛋白,凝胶银染显色,ImageMaster2D图像分析系统分析,从凝胶中选取分离较好的蛋白质点,应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术和数据库搜索鉴定蛋白质。结果:获得了背景清晰、分辨率和重复性较好的双向凝胶电泳图谱,三块胶平均蛋白质点数为1506±74,匹配点数为1412±56,匹配率达93.4%,三块胶蛋白质点在位置上有较好的重复性,不同胶间蛋白质点在IEF方向偏差是(0.96±0.27)mm,在SDS-PAGE方向偏差是(1.24±0.41)mm。胶内酶解-肽质指纹图分析鉴定了58个蛋白质,其中有原癌蛋白、细胞周期调控和信号转导相关蛋白质。结论:建立了小细胞肺癌细胞系NCI-H446双向电泳参考图谱,并应用质谱技术鉴定了部分蛋白质点,为进一步构建其蛋白质表达数据库提供了基础。     

The x c − cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine

Purpose  To determine whether the x_c⁻ cystine transporter could be a useful therapeutic target for small-cell lung cancer (SCLC). Methods  Human SCLC cell cultures were examined for growth dependence on extracellular cystine, x_c⁻ expression, glutathione levels and response to highly specific x_c⁻ inhibitors, i.e., monosodium glutamate (MSG) and the anti-inflammatory drug, sulfasalazine (SASP). In studying tumor growth inhibition by SASP, use was also made of a novel SCLC tissue xenograft model, LU6-SCLC, derived from a chemoresistant patient’s SCLC specimen. Results  Growth of NCI-H69 and NCI-H82 SCLC cells greatly depended on x_c⁻-mediated uptake of cystine. SASP substantially reduced their glutathione levels (>70%; 0.3 mM SASP; 24 h) and growth (72 h) with IC₅₀s of 0.21 and 0.13 mM, respectively; MSG also inhibited growth markedly. Both SASP- and MSG-induced growth arrests were largely prevented by cystine uptake-enhancing 2-mercaptoethanol (66 μM) indicating they were primarily due to cystine starvation. Without major side-effects, SASP (i.p.) restrained growth of NCI-H69 cell xenografts (~50%) and, importantly, substantially inhibited growth of the clinically more relevant LU6-SCLC tissue xenografts (~70% by stereological analysis), reducing tumor glutathione contents. Conclusions  The x_c⁻ cystine/glutamate antiporter is potentially useful as a target for therapy of SCLC based on glutathione depletion. Sulfasalazine may be readily used for this approach, especially in combination chemotherapy.     

重组人血管内皮抑制素联合EP方案对小细胞肺癌细胞株NCI-H446的增殖抑制和促细胞凋亡作用

目的:本研究旨在评估依托泊苷(etoposide,VP-16)、顺铂(cisplatin,DDP)(EP方案)联合重组人血管内皮抑制素对小细胞肺癌(small-cell lung cancer,SCLC) NCI-H446细胞的促凋亡和抑制细胞增殖的协同作用.方法:EP方案、重组人血管内皮抑制素单药以及EP方案联合重组人血管内皮抑制素作用于NCI-H446细胞72 h后,采用CCK-8(cell counting kit-8)法测定药物对NCI-H446细胞的增殖抑制作用,FCM检测药物对NCI-H446细胞的细胞周期分布的影响,ELISA法检测药物对NCI-H446细胞分泌血管内皮细胞生长因子(vascularendothelial cell growth factor,VEGF)水平的影响.结果:EP方案联合重组人血管内皮抑制素的细胞增殖抑制率明显高于EP方案组(P＜0.01).EP方案组和EP方案联合重组人血管内皮抑制素组的NCI-H446细胞大多被阻滞于G1期,EP方案联合重组人血管内皮抑制素组的NCI-H446细胞凋亡率显著高于EP方案组(P＜0.01).与EP方案和重组人血管内皮抑制素单药相比,EP方案联合重组人血管内皮抑制素可显著抑制NCI-H446细胞分泌VEGF(P＜0.05).结论:EP方案联合重组人血管内皮抑制素在抑制SCLC NCI-H446细胞增殖和促细胞凋亡方面,具有协同作用.     

HIF-1α effects on angiogenic potential in human small cell lung carcinoma

Background

Hypoxia-inducible factor-1 alpha (HIF-1α) maybe an important regulatory factor for angiogenesis of small cell lung cancer (SCLC). Our study aimed to investigate the effect of HIF-1α on angiogenic potential of SCLC including two points: One is the effect of HIF-1α on the angiogenesis of SCLC in vivo. The other is the regulation of angiogenic genes by HIF-1α in vitro and in vivo.

Methods

In vivo we used an alternative method to study the effect of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell transplantation tumor on the chick embryo chorioallantoic membrane (CAM) surface. In vitro we used microarray to screen out the angiogenic genes regulated by HIF-1a and tested their expression level in CAM transplantation tumor by RT-PCR and Western-blot analysis.

Results

In vivo angiogenic response surrounding the SCLC transplantation tumors in chick embryo chorioallantoic membrane (CAM) was promoted after exogenous HIF-1α transduction (p < 0.05). In vitro the changes of angiogenic genes expression induced by HIF-1α in NCI-H446 cells were analyzed by cDNA microarray experiments. HIF-1α upregulated the expression of angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26-, 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98-, 3.74- fold respectively. In addition, the expression of these angiogenic factors were also upregulated by HIF-1α in the transplantion tumors in CAM as RT-PCR and Western-blot analysis indicated.

Conclusions

These results indicated that HIF-1α may enhance the angiogenic potential of SCLC by regulating some angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1α may be a potential target for the gene targeted therapy of SCLC.     

Apoptosis in cancer: from pathogenesis to treatment

Background

Hypoxia-inducible factor-1 alpha (HIF-1α) maybe an important regulatory factor for angiogenesis of small cell lung cancer (SCLC). Our study aimed to investigate the effect of HIF-1α on angiogenic potential of SCLC including two points: One is the effect of HIF-1α on the angiogenesis of SCLC in vivo. The other is the regulation of angiogenic genes by HIF-1α in vitro and in vivo.

Methods

In vivo we used an alternative method to study the effect of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell transplantation tumor on the chick embryo chorioallantoic membrane (CAM) surface. In vitro we used microarray to screen out the angiogenic genes regulated by HIF-1a and tested their expression level in CAM transplantation tumor by RT-PCR and Western-blot analysis.

Results

In vivo angiogenic response surrounding the SCLC transplantation tumors in chick embryo chorioallantoic membrane (CAM) was promoted after exogenous HIF-1α transduction (p < 0.05). In vitro the changes of angiogenic genes expression induced by HIF-1α in NCI-H446 cells were analyzed by cDNA microarray experiments. HIF-1α upregulated the expression of angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26-, 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98-, 3.74- fold respectively. In addition, the expression of these angiogenic factors were also upregulated by HIF-1α in the transplantion tumors in CAM as RT-PCR and Western-blot analysis indicated.

Conclusions

These results indicated that HIF-1α may enhance the angiogenic potential of SCLC by regulating some angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1α may be a potential target for the gene targeted therapy of SCLC.     

血管内皮生长因子C过表达或抑制表达对人小细胞肺癌NCI-H446细胞生物学行为的影响

目的:探讨血管内皮生长因子C (vascular endothelial growth factor C,VEGF-C)对人小细胞肺癌细胞株NCI-H446生长、体外侵袭和细胞凋亡的影响.方法:构建VEGF-C过表达慢病毒质粒pHRi-VEGF-C和小干扰RNA(small interference RNA,siRNA)慢病毒表达质粒pHRi-siVEGF-C,经慢病毒包装后分别感染NCI-H446细胞.蛋白质印迹法检测VEGF-C的表达水平,MTT方法检测细胞增殖活性,Transwell实验检测细胞体外侵袭能力,FCM检测细胞凋亡比例.结果:与空载体对照组相比,pHRi-VEGF-C质粒感染入NCI-H446细胞后VEGF-C基因表达水平显著升高,而pHRi-siVEGF-C质粒感染后VEGF-C基因表达水平显著降低.pHRi-VEGF-C质粒感染第5天后,NCI-H446细胞增殖(D值=1.481±0.056)明显高于pHRi-siVEGF-C组(D值=0.838±0.035)和空载体对照组(D值=1.146±0.07),差异有统计学意义(P＜0.05); pHRi-siVEGF-C组中每个视野侵袭的细胞平均数为39.78±0.77,显著低于pHRi-VEGF-C组的84.87±1.27和空载体对照组的60.82±1.05,差异有统计学意义(P＜0.01).感染了pHRi-VEGF-C质粒后的NCI-H446细胞凋亡数较空载体对照组减少约90％,差异有统计学意义(P＜0.01).结论:VEGF-C过表达可以显著促进NCI-H446细胞增殖,增强其侵袭能力,抑制细胞凋亡;而VEGF-C表达经RNA干扰后可以显著减缓细胞的增殖趋势,降低NCI-H446细胞的侵袭能力.推测VEGF-C可能成为临床治疗小细胞肺癌的基因治疗靶点之一.