Gene Therapy For Lung Cancer Research Articles

Inhaled Gene Therapy in Lung Cancer: Proof-Of-Concept for Nano-Oncology and Nanobiotechnology in the Management of Lung Cancer

Lung cancer still remains one of the leading causes of death among cancer patients. Although novel targeted therapies have been established in everyday treatment practice, and conventional platinum-based doublets have demonstrated effective results regarding overall and progression-free survival, we have still failed to achieve long-term survival. Therefore, several strategies of applying locoregional therapy are under investigation. Aerosol chemotherapy is already under investigation and, taking this a step further, aerosol gene therapies with multiple delivery systems are being developed. Several efforts have demonstrated its efficiency and effectiveness, but there are still multiple factors that have to be considered and combined to achieve an overall more effective multifunctional treatment. In the current review, we present data regarding aerosol delivery systems, transporters, carriers, vectors, genes, toxicity, efficiency, specificity, lung microenvironment and delivery gene therapy systems. Finally, we present current studies and future perspectives.

Overexpression of beclin1 induced autophagy and apoptosis in lungs of K-rasLA1 mice

Beclin1, as a key molecule in controlling autophagy pathway, can activate both cell survival and cell death pathway. As a role of autophagy in cancer progression remains controversial, introduction of beclin1 to the lungs of K-rasLA1 mice was performed via inhalation. Prolonged autophagy activation was induced by repeated exposure of lentivirus-beclin1, total of 8 times (2 times/week, 4 weeks). By the time of sacrifice, lungs were collected and analyzed for the therapeutic efficacy. Total numbers of tumors on the surface and histopathological tumor progression were reduced in the lungs of K-rasLA1 mice. Successful delivery of beclin1 induced autophagy and apoptosis in the target organ, which were confirmed by following features; increased autophagic vacuoles in the cytosol, increased number of mitochondria with decreased mitochondrial 12S RNA, and increased protein levels of mitochondria-related apoptosis. Markers for cell proliferation and angiogenesis, PCNA and VEGF, which used for prediction of cancer prognosis, were significantly reduced after introduction of beclin1. Taken together, the results indicate that autophagy regulating gene, beclin1, can be a potential target for lung cancer gene therapy.

Comparative analysis of the transduction efficiency of five adeno associated virus serotypes and VSV-G pseudotype lentiviral vector in lung cancer cells

BackgroundLung cancer is the leading cause of cancer-related deaths in the US. Recombinant vectors based on adeno-associated virus (AAV) and lentivirus are promising delivery tools for gene therapy due to low toxicity and long term expression. The efficiency of the gene delivery system is one of the most important factors directly related to the success of gene therapy.MethodsWe infected SCLC cell lines, SHP-77, DMS 53, NCI-H82, NCI-H69, NCI-H727, NCI-H1155, and NSCLC cell lines, NCI-H23, NCI-H661, and NCI-H460 with VSV-G pseudo-typed lentivirus or 5 AAV serotypes, AAV2/1, AAV2/2, AAV2/4, AAV2/5, and AAV2/8 expressing the CMV promoter mCherry or green fluorescent protein transgene (EGFP). The transduction efficiency was analyzed by fluorescent microscopy and flow cytometry.ResultsOf all the serotypes of AAV examined, AAV2/1 was the optimal serotype in most of the lung cancer cell lines except for NCI-H69 and NCI-H82. The highest transduction rate achieved with AAV2/1 was between 30–50% at MOI 100. Compared to all AAV serotypes, lentivirus had the highest transduction efficiency of over 50% at MOI 1. Even in NCI-H69 cells resistant to all AAV serotypes, lentivirus had a 10-40% transduction rate. To date, AAV2 is the most widely-used serotype to deliver a transgene. Our results showed the transduction efficiency of AAVs tested was AAV2/1 > AA2/5 = AAV2/2> > AAV2/4 and AAV2/8.ConclusionsThis study demonstrated that VSV-G pseudotyped lentivirus and AAV2/1 can mediate expression of a transgene for lung cancer gene therapy. Overall, our results showed that lentivirus is the best candidate to deliver a transgene into lung cancer cells for treatment.

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

Due to their chemoattractant properties stimulating the accumulation of infiltrating immune cells in tumors, chemokines are known to have antitumor effects. Fractalkine, a unique CX3C chemokine, is expressed in activated endothelial cells, while its receptor, CX3CR1, is expressed in cytolytic immune cells, such as natural killer cells, monocytes and some CD8+ T cells. The biological properties of cancer cells are affected by the implantation organ and differences in immune systems, requiring cancer implantation in orthotopic organs in an in vivo experiment. To develop new therapy strategies for lung cancer, an animal model reflecting the clinical features of lung cancer was previously established. This study aimed to determine whether CX3CL1-induced biological functions should be used for immune cell-based gene therapy of lung cancer in the orthotopic implantation model. An orthotopic intrapulmonary implantation of CX3CL1-stable expression in mouse lung cancer (LLC-CX3CL1) was performed to analyze growth. Results showed a significant decrease in tumor growth in the lung compared to the control cells (LLC-mock). Furthermore, the antitumor effects of CX3CL1 were derived from natural killer cell activities in the depletion experiment in vivo. Therefore, CX3CL1 has the potential of a useful therapeutic target in lung cancer.

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer.

Inhaled Gene Therapy in Lung Cancer: “as for the future, Our Task is Not to Foresee it, But to Enable it”

Inhaled Gene Therapy in Lung Cancer: “as for the future, Our Task is Not to Foresee it, But to Enable it”

Management of malignant pleural effusion by suicide gene therapy in advanced stage lung cancer: a case series and literature review

Gene therapy can be defined as the transfer of genetic material into a cell for therapeutic purposes. Cytosine deaminase (CD) transferred into tumor cells by an adenoviral vector (Ad.CD), can convert the antifungal drug fluorocytosine (5-FC) to the antimetabolite 5-fluorouracil (5-FU), which kills not only the transfected tumor cells but also their neighbors by the so-called 'bystander effect'. After testing a protocol for Ad.CD transfer and lung tumor burden control in a Lewis mouse model, we used this technique in the management of lung cancer patients with malignant pleural effusion (MPE): two cases are presented investigating the possible enhancement of anticancer effect in both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) by local activation of the pro-drug 5-FC. Results were discussed in parallel to a literature review on the topic. 5-FC and Ad.CD were administered intratumorally to Lewis mouse lung carcinoma and the effect was monitored by tumor size and electromicroscopy. Two patients with advanced stage lung cancer (1SCLC, 1NSCLC), which developed MPE during first-line treatment were administered 10(12) plaque-forming unit (pfu) Ad.CD by intrapleural instillation, in two doses (day 1 and day 7). Instillation was performed when the pleural fluid was ≤200 ml. In addition, they received 5-FC 500 mg four times daily for 14 days. Lung tumor regression and successful transfer of adenoviral particles were observed in treated animals. Patients presented complete regression of pleural effusion as monitored by computerized tomography scan. Neutrapenia and anemia were the most severe adverse effect presented (grade III/grade IV 100%). The increased toxicity followed by the intrapleural gene therapy indicates the augmentation of anticancer effect of transformed pro-drug 5-FC to active 5-FU. The obtained data indicate that intrapleural gene therapy may be a useful tool, adjunct to chemotherapy, in the management of MPE related to lung cancer.

Intratracheal Administration of a Nanoparticle-Based Therapy with the Angiotensin II Type 2 Receptor Gene Attenuates Lung Cancer Growth

Targeted gene delivery, transfection efficiency, and toxicity concerns remain a challenge for effective gene therapy. In this study, we dimerized the HIV-1 TAT peptide and formulated a nanoparticle vector (dTAT NP) to leverage the efficiency of this cell-penetrating strategy for tumor-targeted gene delivery in the setting of intratracheal administration. Expression efficiency for dTAT NP-encapsulated luciferase or angiotensin II type 2 receptor (AT2R) plasmid DNA (pDNA) was evaluated in Lewis lung carcinoma (LLC) cells cultured in vitro or in vivo in orthotopic tumor grafts in syngeneic mice. In cell culture, dTAT NP was an effective pDNA transfection vector with negligible cytotoxicity. Transfection efficiency was further increased by addition of calcium and glucose to dTAT/pDNA NP. In orthotopic tumor grafts, immunohistochemical analysis confirmed that dTAT NP successfully delivered pDNA to the tumor, where it was expressed primarily in tumor cells along with the bronchial epithelium. Notably, gene expression in tumor tissues persisted at least 14 days after intratracheal administration. Moreover, bolus administration of dTAT NP-encapsulated AT2R or TNF-related apoptosis-inducing ligand (TRAIL) pDNA markedly attenuated tumor growth. Taken together, our findings offer a preclinical proof-of-concept for a novel gene delivery system that offers an effective intratracheal strategy for administering lung cancer gene therapy.

Abstract 5653: A novel cationic peptide nanoparticle-based gene therapy with angiotensin II type 2 receptor gene significantly attenuates growth of lung adenocarcinoma xenografts in mouse model

Abstract A successful gene therapy requires targeted gene delivery, high gene transfection efficiency at the target tissue, and low toxicity of the vectors. We have demonstrated that the HIV-1 TAT peptide is suggested to be an effective gene delivery vector in various cultured cells (Baoum, et al., Pharm Res, 2009; Baoum, et al., Int J Pharm, 2011). The objectives of the present study were to examine the gene transfection efficacy of modified TAT peptide nanoparticle (two TAT peptides connected in tandem i.e. dTAT NP) as a vector, and to examine the efficiency of the tumor-targeted gene delivery after intratracheal administration. Expression efficiency of the dTAT NP encapsulating luciferase or angiotensin II type 2 receptor (AT2R) plasmid DNA (pDNA) was evaluated using Lewis Lung carcinoma (LLC) cells in culture and orthotopic autografts in C57BL/6 mice lungs. Cell culture studies clarified that the dTAT NP caused effective gene transfection with negligible cytotoxicity until approximately 4 mg dTAT/mL (IC50= 4.075 mg/mL), whereas polyethyleneimine (PEI) showed much stronger cytotoxicity (IC50= 0.028 mg/mL). The in vitro study also revealed that the addition of calcium and glucose to the dTAT/pDNA NP caused effective DNA transfection. The in vitro transfection of pAT2R by dTAT NP caused marked attenuation of the growth of LLC cells. Immunohistochemical analysis of the in vitro transfection and in vivo mouse gene expression studies with dTAT/luciferase pDNA NP revealed that dTAT NP vector successfully delivered the dTAT/pDNA complex to the tumor tissues and caused gene expression primarily in the tumor cells and bronchial epithelium. Gene expression in the tumor tissues lasted for at least 14 days post-administration. Bolus intratracheal administration of dTAT/pAT2R as well as dTAT/pTRAIL markedly attenuated tumor growth of LLC autografts in the mouse lungs. Immunohistochemical analysis of dissected tumors revealed that the AT2R expression was predominantly located in the tumor cells of the LLC tumor bearing mouse lung. Apoptotic index was significantly higher in the treated tumors than PBS or luciferase treated control tumors, suggesting that AT2R pDNA was successfully delivered to the tumor tissues by dTAT NP vector and caused apoptosis of tumor cells. Taken together, the current study suggests that a gene delivery system using intratracheal administration of dTAT/pAT2R NP offers an effective strategy for lung cancer gene therapy. This work was supported by the Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU College of Veterinary Medicine Dean's Fund, NIH P20 RR017686, p20 RR1556, R21CA135599 and Kansas Bioscience Authority Collaborative Cancer Research grant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5653. doi:1538-7445.AM2012-5653

Suppression of lung cancer progression by biocompatible glycerol triacrylate– spermine-mediated delivery of shAkt1

BackgroundPolyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate–spermine (GT–SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy.MethodsThe GT–SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance.ResultsThe GT–SPE successfully protected the DNA from nucleases. The average particle size of the GT–SPE was 121 nm with a zeta potential of +23.45 mV. The GT–SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT–SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-rasLA1 lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT–SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively.ConclusionOur data suggest that GT–SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy.

Effect of shRNA Survivin-mediated inhibition of proliferation in A549 cells

背景与目的Survivin是凋亡抑制蛋白(inhibitor of apoptosis protein, IAP)家族的成员, 在多种肿瘤组织中高度表达而在终末分化细胞中极少表达, 因此可以作为癌症治疗的理想靶点。本研究旨在通过构建Survivin基因shRNA的慢病毒质粒并干扰肺癌细胞A549中Survivin的表达, 分析其对细胞增殖的影响。方法设计Survivin干扰靶序列, 构建重组质粒; 将pLL3.7-Survivin转染293T细胞后利用Hela细胞检测病毒的滴度并感染A549细胞, 应用RT-PCR和Western blot检测干扰效果; MTT与流式细胞术分析其对细胞增殖的影响。结果本研究成功构建了重组质粒; 重组质粒可抑制A549细胞中Survivin基因的表达; 细胞受阻于G2/M期。结论本研究构建的重组质粒可抑制Survivin基因的表达并影响细胞的增殖, 其为研究RNAi介导的肺癌基因治疗打下基础。

Research on anti-sense nucleotide technology in current lung cancer treatment

Lung cancer has been widely known for its highest morbidity among all tumors in this world.Anti-sense neoclitide technology is a kind of widely-recognized gene therapy for its high efficiency and practical simplicity.This essay will briefly review principles of anti-sense neoclitide technology used in treatment of lung cancer and characteristics of this technology in gene therapy of lung cancer. Key words: Oligoribonucleotides, antisense; Lung neoplasms; Genes

Current status and prospect of lung cancer gene therapy

Current Status and Prospect of Lung Cancer Gene Therapy Lingling ZU, Hongyu LIU, Jun CHEN, Qinghua ZHOU Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China Corresponding author: Jun CHEN, E-mail: huntercj2004@yahoo.com; Qinghua ZHOU, E-mail: zhouqh1016@yahoo.com.cn This study was supported by grants from the National Natural Science Foundation of China (to Qinghua ZHOU)(No.30972963), China-Sweden Cooperative Foundation (to Qinghua ZHOU)(No.09ZCZDSF04100, No.09ZCZDSF04000, No.09ZCZDSF03800), Tianjin Natural Science Foundation (to Qinghua ZHOU) (No.09JCYBJC1620 0) and Wujieping Foundation (to Qinghua ZHOU)(No.320672010008). DOI: 10.3779/j.issn.1009-3419.2011.09.11

Aerosol delivery of spermine-based poly(amino ester)/Akt1 shRNA complexes for lung cancer gene therapy

Polyethylenimine (PEI) has been commonly used as a cationic polymeric gene carrier due to high transfection efficiency, however, its cytotoxicity has hindered the practical application. In this study, we report the development of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) as an alternative gene carrier for lung cancer therapy. GPT–SPE copolymer was prepared by Michael addition reaction between GPT and SPE, and the efficacy was evaluated using shAkt1 as a model therapeutic gene. The molecular weight and composition were characterized using gel permeability chromatography (GPC) and 1H-nuclear magnetic resonance ( 1H-NMR), respectively. The GPT–SPE could effectively condense DNA with about 163 nm size and protect the DNA from nucleases. GPT–SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo. Furthermore, aerosol delivery of GPT–SPE/Akt1 shRNA complexes significantly suppressed lung tumorigenesis in K- ras LA1 lung cancer model mice. These results suggest that GPT–SPE can be used in shRNA-based lung cancer gene therapy.

Downregulation and growth inhibitory role of FHL1 in lung cancer

Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10(-4) ) and the differentiation of the tumor (p = 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.

A novel cationic liposome formulation for efficient gene delivery via a pulmonaryroute

The clinical success of gene therapy for lung cancer is not only dependent on efficient genecarriers but also on a suitable delivery route. A pulmonary delivery route can directlydeliver gene vectors to the lung which is more efficient than a systemic delivery route. Forgene carriers, cationic liposomes have recently emerged as leading non-viral vectors inworldwide gene therapy clinical trials. However, cytotoxic effects or apoptosis are oftenobserved which is mostly dependent on the cationic lipid used. Therefore, an efficient andsafe cationic lipid, 6-lauroxyhexyl lysinate (LHLN), previously synthesized by our groupwas first used to prepare cationic liposomes. Physicochemical and biological properties ofLHLN-liposomes were investigated. LHLN-liposome/DNA complexes showed positivesurface charge, spherical morphology, a relatively narrow particle size distributionand strong DNA binding capability. Compared with Lipofectamine2000, the newcationic liposome formulation using LHLN exhibited not only lower cytotoxicity(P < 0.05) but also similar transfection efficiency in A549 and HepG2 lung cancer cellsfor in vitro tests. When administered by intratracheal instillation into ratlungs for in vivo evaluation, LHLN-liposome/DNA complexes exhibited higherpulmonary gene transfection efficiency than Lipofectamine2000/DNA complexes (P < 0.05). These results suggested that LHLN-liposomes may have great potential for efficientpulmonary gene delivery.

Effects of human Livin gene down-regulation by RNA interference on xenograft of transplantation tumor induced by SPC-A1 in nude mice

To explore the in vivo inhibitory effect of Livin gene silencing by RNA interference on xenograft of lung adenocarcinoma SPC-A-1 cells in BALB/C nude mice. Three different BALB/C nude mice models were established by subcutaneously inoculating differently treated SPC-A-1 cells into 3 nude mice groups: the blank control group was inoculated with blank SPC-A-1 cells, while the negative group was inoculated with cells transfected with lentivirus-delivered negative shRNA, the experimental group was inoculated with cells with lentivirus-delivered Livin shRNA. Then the growth of tumors was observed, and the volume and weight of the tumors were measured at different time points. The curve of tumor growth was then described, and the inhibition rate was calculated. Livin gene expression in the tumor tissues was determined by RT-PCR and Immunohistochemistry. Cell apoptosis of tumor tissues was detected by TUNEL. Slower tumor growth, smaller tumor volume and lighter tumor weight were observed in the experimental group as compared to the blank and negative groups (F = 70.509, P < 0.01; F = 12.821, P < 0.01). The inhibition rate of tumor volume was (59.5 ± 3.4)%, and the inhibition rate of tumor weight was (71.1 ± 5.6)%. Livinα mRNA and Livinβ mRNA expressions in the experimental group were significantly lower than the 2 control groups [(37.2 ± 1.6)% versus (63.3 ± 3.8)%, (66.1 ± 2.6)%; (29.4 ± 1.1)% versus (53.2 ± 3.4)%, (52.3 ± 3.1)% (F(α) = 45.309, P < 0.01; F(β) = 30.076, P < 0.01)]. Livin protein expression level was also significantly lower than the blank and the negative groups [(15.3 ± 2.8)% versus (51.3 ± 2.1)%, (52.5 ± 2.5)%, F = 78.92, P < 0.01]. The apoptosis rate in the experimental group was significantly higher than that in the 2 control groups [(35.4 ± 3.2)% versus (5.4 ± 1.3)%, (8.6 ± 1.5)%, F = 14.509, P < 0.01]. The lentivirus-delivered Livin shRNA was shown to inhibit the proliferation of transplantation tumor of lung carcinoma effectively, and Livin may be a target for gene therapy in lung cancer.

Adenovirus-mediated SOCS3 gene transfer inhibits the growth and enhances the radiosensitivity of human non-small cell lung cancer cells

The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is one of the most important components of cytokine signaling cascades. JAK-STAT signaling pathway modulates various fundamental biological processes and cancer pathogenesis. JAK-STAT is controlled by negative regulators that include suppressors of cytokine signaling (SOCS) proteins. Failure of feedback suppression by SOCS proteins may result in activated JAK-STAT signaling. Methylation-mediated silencing of SOCS3 has been reported in non-small lung cancer (NSCLC) and other human cancers. In this study, we restored SOCS3 expression using adenovirus-mediated gene transfer in NSCLC cells. Infection with a SOCS3-expressing vector inhibited the growth of lung cancer cells, with or without SOCS3 expression, at 2-3 days after infection. The growth inhibition of lung cancer cells was associated with suppressing entry into the S-phase. Restoration of SOCS3 expression induced apoptosis of NSCLC cells that did not express SOCS3. In addition, overexpression of SOCS3 by adenoviral transfer enhanced the radiosensitivity of treated NSCLC cells. In conclusion, our findings may provide insights into the development of applications of SOCS3 gene therapy for lung cancer and, possibly, other human cancers.

206. Effect of Transcriptionally Targeted Suicide Gene Therapy for Small Cell Lung Cancer In Vitro and In Vivo by DOTAP/Cholesterol- and Adenoviral-Mediated Delivery

206. Effect of Transcriptionally Targeted Suicide Gene Therapy for Small Cell Lung Cancer In Vitro and In Vivo by DOTAP/Cholesterol- and Adenoviral-Mediated Delivery

A small interfering ABCE1-targeting RNA inhibits the proliferation and invasiveness of small cell lung cancer

Small cell lung cancer (SCLC) is a highly aggressive lung neoplasm. To study the pathogenesis of SCLC, we investigated roles of ABCE1, a member of the ATP-binding cassette (ABC) superfamily, in the development of small cell lung cancer. RNA interference was used to knock down ABCE1 expression in human small cell lung cancer cell lines (NCI-H446). Then we examined the effects of ABCE1 knockdown in cancer cells, including proliferation, invasiveness, apoptosis, and gene expression. We found that ABCE1 could be efficiently knocked down by siRNA, and the ABCE1 silence inhibited the proliferation, invasiveness of small cell lung cancer cell lines NCI-H446. In conclusion, our results suggest that ABCE1 play an important role in the pathogenesis of human small cell lung cancer cell. ABCE1 may be used as a potential target of gene therapy for small cell lung cancer in future.