Filamin A Interacting Protein 1-like Research Articles

Long-chain noncoding RNA LINC01569 upregulates filamin A-interacting protein 1-like to prevent metastasis of triple-negative breast cancer via sponging miR-300.

Long-chain noncoding RNA (lncRNA), LINC01569, is important for regulating the extracellular matrix, which affects cell migration. However, its involvement in the occurrence and development of triple-negative breast cancer (TNBC) remains unclear. This study is aimed to investigate the role of LINC01569 on TNBC. Online database was used for clinical data analysis. Cell viability and migration capability were monitored using cell counting kit-8 and transwell assays, respectively. Luciferase reporter assay and RNA pull-down were used to confirm the binding capability between noncoding RNAs and filamin A-interacting protein 1-like (FILIP1L). Western blotting was used to determine the protein content. Compared with normal breast tissue, LINC01569 was significantly reduced in patients with TNBC subtype, and LINC01569 expression gradually decreased with the progression of tumor stage. Patients with TNBC with high lncRNA LINC01569 levels had a better prognosis than did patients with low LINC01569 levels. LINC01569 overexpression inhibited the migration capability, whereas siRNA-mediated LINC01569 downregulation promoted the migration capability in TNBC cells. Using ENCORI and lncRNA SNP online databases, miR-300 was screened as the potential sponge of LINC01569. The binding of LINC01569 to miR-300 was confirmed using the dual-luciferase reporter and RNA pull-down assays. miR-300 was negatively correlated with LINC01569, and miR-300 mimics eliminated the anti-proliferation and anti-migration effects of LINC01569 on TNBC cells. Additionally, FILIP1L was further verified as the downstream target of miR-300. miR-300 mimics blocked LINC01569 upregulation-mediated elevation of FILIP1L. Importantly, the anti-tumor effects mediated by LINC01569 overexpression were abolished by miR-300 mimics and further restored by FILIP1L upregulation. LINC01569 was expressed at a low level in TNBC and could sponge miR-300 to promote FILIP1L expression, reducing the proliferation and metastasis capability of TNBC. Thus, LINC01569 might be a useful biomarker in the diagnosis and prognosis of metastatic TNBC.

FILIP1L Loss Is a Driver of Aggressive Mucinous Colorectal Adenocarcinoma and Mediates Cytokinesis Defects through PFDN1.

Aneuploid mucinous colorectal adenocarcinoma (MAC) is an aggressive subtype of colorectal cancer with poor prognosis. The tumorigenic mechanisms in aneuploid MAC are currently unknown. Here we show that downregulation of Filamin A-interacting protein 1-like (FILIP1L) is a driver of MAC. Loss of FILIP1L increased xenograft growth, and, in colon-specific knockout mice, induced colonic epithelial hyperplasia and mucin secretion. The molecular chaperone prefoldin 1 (PFDN1) was identified as a novel binding partner of FILIP1L at the centrosomes throughout mitosis. FILIP1L was required for proper centrosomal localization of PFDN1 and regulated proteasome-dependent degradation of PFDN1. Importantly, increased PFDN1, caused by downregulation of FILIP1L, drove multinucleation and cytokinesis defects in vitro and in vivo, which were confirmed by time-lapse imaging and 3D cultures of normal epithelial cells. Overall, these findings suggest that downregulation of FILIP1L and subsequent upregulation of PFDN1 is a driver of the unique neoplastic characteristics in aggressive aneuploid MAC. SIGNIFICANCE: This study identifies FILIP1L as a tumor suppressor in mucinous colon cancer and demonstrates that FILIP1L loss results in aberrant stabilization of a centrosome-associated chaperone protein to drive aneuploidy and disease progression.

Abstract 4718: Filamin A interacting protein 1-like is a marker of prognosis, progression and chemosensitivity in ovarian cancer

Abstract Purpose: The WNT/β-catenin pathway and the resulting epithelial-to-mesenchymal transition (EMT) play a key role in ovarian cancer progression and chemoresistance. Filamin A interacting protein 1-like (FILIP1L) enhances β-catenin degradation, thereby inhibiting canonical WNT signaling and EMT. FILIP1L is a tumor suppressor whose expression is down-regulated by promoter hyper-methylation in ovarian cancer. FILIP1L down-regulation is inversely correlated with the invasive potential of ovarian cancer cells. However, the clinical relevance of FILIP1L down-regulation in ovarian cancer progression has yet to be addressed. Experimental design: To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway and chemoresistance, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic. Their expression was evaluated with clinicopathological characteristics including FIGO stage and chemosensitivity, and correlated with overall and disease-free survival by Kaplan-Meier plots and Cox proportional hazards model. Results: We demonstrated that FILIP1L expression decreased with tumor progression, resulting in a significant difference between primary and metastatic ovarian cancer samples. In contrast, levels of β-catenin and SLUG increased with tumor progression. Furthermore, tumors that were resistant to platinum/paclitaxel combination therapy showed a significant reduction in FILIP1L expression when compared to sensitive tumors, contrary to SLUG expression, which was significantly higher. The expression of FILIP1L was negatively correlated with the expression of β-catenin and SLUG, whereas β-catenin expression was positively correlated with SLUG expression, suggesting a link between FILIP1L and the WNT/β-catenin pathway in ovarian cancer. Moreover, patients with low FILIP1L expression showed a median overall survival and disease-free survival of 60 and 19 months, respectively, whereas patients with high FILIP1L expression had not yet reached median overall and disease-free survival at their 120 month follow-up. Notably, low FILIP1L expression was independent negative prognostic factor with respect to overall and disease-free survival. Conclusions: Our study provides the first clinical relevance of FILIP1L in human cancer, and suggests that FILIP1L may be a novel biomarker for good prognosis and lower probability of recurrence in ovarian cancer patients. Citation Format: Mijung Kwon, Jae-Hoon Kim, Chel Hun Choi, Joon-Yong Chung, Stephen Hewitt, Steven Libutti. Filamin A interacting protein 1-like is a marker of prognosis, progression and chemosensitivity in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2017-4718

Reduced expression of FILIP1L, a novel WNT pathway inhibitor, is associated with poor survival, progression and chemoresistance in ovarian cancer.

Filamin A interacting protein 1-like (FILIP1L) is an inhibitor of the canonical WNT pathway. WNT/β-catenin signaling and its downstream pathway, epithelial-to-mesenchymal transition (EMT), play a key role in ovarian cancer metastasis and chemoresistance. To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic. In addition, the results were validated in mouse model and in vitro cell culture. In the present study, we demonstrated that FILIP1L expression was inversely correlated with poor prognosis, stage and chemoresistance in ovarian cancer. Notably, low FILIP1L expression was independent negative prognostic factor with respect to overall and disease-free survival. FILIP1L inhibited peritoneal metastases in orthotopic mouse model. FILIP1L knockdown induced chemoresistance in ovarian cancer cells and this phenotype was rescued by simultaneous knockdown of FILIP1L and SLUG, an EMT activator. We also demonstrated that FILIP1L regulates β-catenin degradation. FILIP1L co-localizes with phospho-β-catenin and increases phospho-β-catenin at the centrosomes, destined for proteosomal degradation. Finally, we showed that FILIP1L regulates EMT. Overall, these findings suggest that FILIP1L promotes β-catenin degradation and suppresses EMT, thereby inhibiting metastases and chemoresistance. Our study provides the first clinical relevance of FILIP1L in human cancer, and suggests that FILIP1L may be a novel prognostic marker for chemotherapy in ovarian cancer patients. Further, the modulation of FILIP1L expression may have the potential to be a target for cancer therapy.

Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer.

Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-mediated FILIP1L overexpression suppressed tumor cell migration and invasion and induced apoptosis and cell cycle arrest in HCT116 cells. FILIP1L knockdown enhanced angiogenesis by increasing VEGF-A and HIF-1α levels and decreasing angiostatin level. FILIP1L overexpression suppressed angiogenesis by decreasing VEGF-A and -D l level and increasing angiostatin and endostatin levels. Phosphorylated β-catenin levels decreased and phosphorylated Akt and GSK-3β levels increased following FILIP1L knockdown. FILIP1L overexpression had the opposite effects. FILIP1L expression was associated with reductions in tumor size, cell differentiation, lymphovascular invasion, stage, invasion depth and lymph node metastasis, and with longer overall survival. Mean Ki-67 labeling indexes and microvessel density values were lower in FILIP1L-positive tumors than in FILIP1L-negative tumors. These results indicate that FILIP1L suppresses tumor progression by inhibiting cell proliferation and angiogenesis in colorectal cancer.

Abstract PR06: Impact of RAL signal transduction on genetic program and growth control in KRAS- and BRAF-mutated colorectal cells and prognostic potential of pathway-responsive genes in cancer patients

Abstract The EGFR/RAS signaling system plays an imperative role in tumor pathogenesis and therapy response. Downstream effects of the EGFR/RAS signaling axis are mediated by three major pathway branches: the RAF/MAPK, PI3K and RALA pathways. While the RAF/MAPK and PI3K pathways have been extensively characterized in mechanistic, preclinical and clinical studies, the RAL pathway is less well understood. Here we compared RALGTPase activities in three colorectal cancer cell lines by active GTPase pull-down assay and analyzed the effects of transient silencing of RALA expression by siRNA. RALA activity was highest in SW480 [KRAS codon 12 mutation] and HCT116 cells [KRAS codon 13 mutation] and also detectable in HT29 colorectal cancer cells [KRAS wild-type, BRAF V600E mutation]. Silencing of RALA expression strongly diminished the active GTP-bound form of the protein in all cell lines. The proliferation of the two KRAS mutated cell lines was significantly reduced. BRAF mutated cells showed a slight increase in cell death only. Next we interrogated microarrays using RNA prepared from the cell lines treated with siRNA and controls. We identified 550 common genes the expression of which was up-regulated or down-regulated after RALA knock-down (“RALA pathway-responsive genes”). None of them were affected when the RAF/MAPK or PI3K pathways were blocked. To investigate the potential clinical relevance of transcriptional targets regulated by the RALA pathway, we performed a meta-analysis utilizing expression profiles of 1,424 colorectal cancers documented in 8 independent publicly available data sets comprising information on patient survival. Of 19 RALA pathway-responsive genes correlated with progression-free survival, IQGAP1 (IQ-motif containing GTPase-activating protein 1), TOP1 (topoisomerase 1), LGALS1 (lectin galactoside-binding soluble 1), FILIP1L (filamin A-interacting protein 1-like) and TCF4 (transcription factor 4) were identified as the most important RALA pathway targets capable of predicting survival. In conclusion, the RALA pathway impinges on the transcription of a distinct subset of target genes in colorectal cancer cells independent of the KRAS and BRAF mutational status. RALA pathway-responsive genes were unaffected by RAF/MAPK and PI3K signaling. These findings support the concept of a pathway-sensitive modular organization of the transcriptome. In view of the correlation of RAL pathway-responsive genes and patient survival, further investigations of the diagnostic impact in prospective trials and exploitation of therapeutic approaches are warranted. This abstract is also presented as Poster B32. Citation Format: Balazs Gyorffy, Iwona Stelniec-Klotz, Christian Sigler, Attila Szijarto, Yu Qian, Reinhold Schäfer. Impact of RAL signal transduction on genetic program and growth control in KRAS- and BRAF-mutated colorectal cells and prognostic potential of pathway-responsive genes in cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr PR06. doi: 10.1158/1557-3125.RASONC14-PR06

Filamin A interacting protein 1‐like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis

Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified FILamin A Interacting Protein 1-Like (FILIP1L) as an important inhibitor of cell migration and invasion. FILIP1L expression was inversely correlated with the invasive potential of ovarian tumors. In our study, we established an orthotopic ovarian cancer model, wherein FILIP1L expression can be regulated in vivo. Using this model, we observed that expression of FILIP1L in ovarian cancer cells inhibited spontaneous lung metastasis. Experimental lung metastases (established via tail vein injection of cancer cells) as well as the extravasation step of metastasis were not inhibited by FILIP1L, suggesting that FILIP1L inhibits the earlier steps of metastasis such as invasion and intravasation. FILIP1L inhibited matrix metalloproteinase (MMP)-dependent invasion in vivo. MMP3, -7 and -9 were transcriptionally downregulated, and MMP9 protein expression and activity were inhibited in FILIP1L-expressing tumors. Importantly, overexpression of MMP9 compensated for the anti-invasive activity of FILIP1L. Furthermore, our studies suggest that FILIP1L regulates invasion and metastasis by inhibiting components of the WNT signaling pathway. FILIP1L expression reduced the induction of WNT target genes such as MMP3, -7 and -9, and β-catenin-directed transcriptional activity, suggesting inhibition of the canonical WNT pathway. Nuclear β-catenin, an indicator of an active canonical WNT pathway, was reduced in FILIP1L-expressing tumors. Overall, these findings suggest that FILIP1L reduces β-catenin levels, which may lead to the transcriptional downregulation of WNT target genes such as MMPs, resulting in inhibition of metastasis. Modulation of FILIP1L expression has the potential to be a target for cancer therapy.

Isobaric tags for relative and absolute quantitation for preliminarily screening of differential proteins in hippocampus of Ts65Dn mice

Objective To explore the molecular mechanism of hypophrenia induced by Down syndrome (DS).Methods Ts65Dn mice were used as DS animal model.Three female mice and three male mice of three to twelve weeks old were mated.Among the 17 first-generation mice alive,five mice remained Ts65Dn trisomy and 12 mice were normal.Five Ts65Dn mice and five normal mice were selected randomly as Ts65Dn group and control group,and bred till 16 to 18 weeks old for experiments.Differential proteins in hippocampus of mice were tested by isobaric tags for relative and absolute quantitation (iTRAQ).Expressions of the differential proteins in Ts65Dn group were detected compared with those in control group.Results A total of 2805 proteins were identified in hippocampus of Ts65Dn group and control group,and significant differences were observed in the expressions of 374 proteins.Compared with those in control group,expressions of 195 proteins increased and 179 reduced in Ts65Dn group.Sorted by P value from low to high,the seven proteins with the lowest P value were uncharacterized protein C2orf47 homolog,isoform 2 of filamin A-interacting protein 1-like,zinc finger protein,isoform 1 of pericentriolar material 1 protein,SEC23 interacting protein,BAG family molecular chaperone regulator 3 and serpin H1.Conclusions Differential proteins are observed in hippocampus of Ts65Dn mice,perhaps closely correlating to neurological defects.The new technology of iTRAQ helps to screen and identify differential proteins in hippocampus. Key words: Down syndrome; Hippocampus; Proteomics ; Isotope labeling; Disease models,animal

Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers

Identifying key mediators of cancer cell invasion and metastasis is critical to the development of more effective cancer therapies. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important inhibitor of cell migration and invasion in ovarian cancer. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and ovarian cancer specimens. We also demonstrated that DNA methylation in the FILIP1L promoter was a mechanism by which FILIP1L was down-regulated in ovarian cancer. In our present study, we tested this observation in other cancer histologies: breast, colon, lung and pancreatic cancers. Both mRNA and protein expression of FILIP1L were down-regulated in these cancer cells compared with their normal epithelial cells. As in ovarian cancer, DNA methylation is a mechanism by which FILIP1L is down-regulated in these cancer histologies. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in these cancer cells. Further, FILIP1L expression was inversely correlated with the invasive potential of these cancer cells. Re-expression of FILIP1L in FILIP1L-low expressing, highly-invasive cancer cell lines resulted in inhibition of cell invasion. Correspondingly, knockdown of FILIP1L in FILIP1L-high expressing, low-invasive cancer cell lines resulted in increase of cell invasion. Overall, these findings suggest that down-regulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in various cancers. Thus, modulation of FILIP1L expression has the potential to be a target for cancer therapy.

Abstract A61: Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to suppress ovarian cancer cell invasion and metastasis

Abstract Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important mediator of cell migration and invasion. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and ovarian cancer specimens. In addition, it was shown that intraperitoneal delivery of the FILIP1L gene resulted in inhibition of metastatic ovarian cancer spread into the peritoneum and intra-abdominal organs. Although these observations demonstrate that FILIP1L inhibits metastasis, it is not clear which step(s) of metastasis is inhibited by FILIP1L. To this end, in our present study we chose an orthotopic ovarian cancer model in mice where cancer cells metastasize to distant organs such as lungs which lung metastasis can occur through vessels, not by exfoliation and peritoneal spread. In addition, FILIP1L expression was controlled by a doxycycline-inducible expression system which enabled us to determine the direct effect of FILIP1L expression in vivo. Using this model, we observed that expression of FILIP1L in ovarian cancer cells inhibited spontaneous lung metastasis. Experimental lung metastases (established via tail vein injection of cancer cells) as well as the extravasation step of metastasis were not inhibited by FILIP1L, suggesting that FILIP1L inhibits the earlier steps of metastasis such as invasion and intravasation. FILIP1L inhibited matrix metallo¬proteinase (MMP)-dependent invasion in vivo. MMP3, -7 and -9 were transcriptionally down-regulated, and MMP9 protein expression and activity were inhibited in FILIP1L-expressing tumors. Furthermore, our studies suggest that FILIP1L regulates invasion and metastasis by inhibiting components of the WNT signaling pathway. FILIP1L expression reduced the induction of WNT target genes such as MMP3, -7 and -9, and β-catenin-directed transcriptional activity, suggesting inhibition of the canonical WNT pathway. Nuclear β-catenin, an indicator of an active canonical WNT pathway, was reduced in FILIP1L-expressing tumors. We conclude that FILIP1L reduces β-catenin levels, which leads to the transcriptional down-regulation of WNT target genes such as MMPs, resulting in inhibition of metastasis. Thus, modulation of FILIP1L expression has the potential to be a target for cancer therapy. Citation Format: Mijung Kwon, Soo Jin Lee, Yarong Wang, Yevangelina Ryvak, Alex Luna, Srilakshmi Reddy, Asha Adem, Brian Beaty, John Condeelis, Steven Libutti. Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to suppress ovarian cancer cell invasion and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A61.

Sensitivity to TOP2 Targeting Chemotherapeutics Is Regulated by Oct1 and FILIP1L

Topoisomerase II (TOP2) targeting drugs like doxorubicin and etoposide are frontline chemotherapeutics for a wide variety of solid and hematological malignancies, including breast and ovarian adenocarcinomas, lung cancers, soft tissue sarcomas, leukemias and lymphomas. These agents cause a block in DNA replication leading to a pronounced DNA damage response and initiation of apoptotic programs. Resistance to these agents is common, however, and elucidation of the mechanisms causing resistance to therapy could shed light on strategies to reduce the frequency of ineffective treatments. To explore these mechanisms, we utilized an unbiased shRNA screen to identify genes that regulate cell death in response to doxorubicin treatment. We identified the Filamin A interacting protein 1-like (FILIP1L) gene as a crucial mediator of apoptosis triggered by doxorubicin. FILIP1L shares significant similarity with bacterial SbcC, an ATPase involved in DNA repair. FILIP1L was originally described as DOC1, or “down-regulated in ovarian cancer” and has since been shown to be downregulated in a wide variety of human tumors. FILIP1L levels increase markedly through transcriptional mechanisms following treatment with doxorubicin and other TOP2 poisons, including etoposide and mitoxantrone, but not by the TOP2 catalytic inhibitors merbarone or dexrazoxane (ICRF187), or by UV irradiation. This induction requires the action of the OCT1 transcription factor, which relocalizes to the FILIP1L promoter and facilitates its expression following doxorubicin treatment. Our findings suggest that the FILIP1L expression status in tumors may influence the response to anti-TOP2 chemotherapeutics.

Downregulation of Filamin A Interacting Protein 1-Like is Associated with Promoter Methylation and Induces an Invasive Phenotype in Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy with a five-year survival rate below 25% for patients with stages III and IV disease. Identifying key mediators of ovarian cancer invasion and metastasis is critical to the development of more effective therapeutic interventions. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important mediator of cell proliferation and migration. In addition, targeted expression of FILIP1L in tumors inhibited tumor growth in vivo. In our present study, we confirmed that both mRNA and protein expression of FILIP1L were downregulated in ovarian cancer cells compared with normal ovarian epithelial cells. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and clinical ovarian cancer specimens. We also provide evidence that DNA methylation is a mechanism by which FILIP1L is downregulated in ovarian cancer. The CpG island in the FILIP1L promoter was heavily methylated in ovarian cancer cells. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression in ovarian cell lines and clinical ovarian specimens. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in ovarian cancer cells. A transcription activator, cAMP-responsive element binding protein (CREB) was shown to bind to the CREB/ATF site in the CpG island of the FILIP1L promoter. Overall, these findings suggest that downregulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in ovarian cancer and that modulation of FILIP1L expression has the potential to be a target for ovarian cancer therapy.

Efficient Inhibition of Ovarian Cancer by Truncation Mutant of FILIP1L Gene Delivered by Novel Biodegradable Cationic Heparin-Polyethyleneimine Nanogels

Filamin A interacting protein 1-like (FILIP1L), which was reported to be consistently absent in ovarian cancer cell lines, has been identified to hold therapeutic potential for inhibiting tumor growth, and its COOH-terminal truncation mutant (FILIP1LΔC103) was found to be more potent than the wild-type. The use of polymeric nanoparticles to deliver functional gene intraperitoneally holds much promise as an effective therapy for ovarian cancer. In this study, a recombinant plasmid expressing FILIP1LΔC103 (FILIP1LΔC103-p) was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels were prepared to deliver FILIP1LΔC103-p into human ovarian cancer SKOV3 cells. The expression of FILIP1LΔC103 in vitro and in vivo was determined using RT-PCR and western blot analysis. Moreover, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the antitumor activity of HPEI+FILIP1LΔC103-p complexes in nude mice. Tumor weights were evaluated during the treatment course. Cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay, respectively, and the antiangiogenic effect of FILIP1LΔC103-p was assessed by CD31 immunochemical staining and alginate-encapsulated tumor cell assay. FILIP1LΔC103-p could be efficiently transfected into SKOV3 cells by HPEI nanogels. Intraperitoneal administration of HPEI+FILIP1LΔC103-p complexes led to effective growth inhibition of ovarian cancer, in which tumor weight decreased by almost 72% in the treatment group compared with that in the empty-vector control group. Meanwhile, decreased cell proliferation, increased tumor cell apoptosis, and reduction in angiogenesis were observed in the HPEI+FILIP1LΔC103-p group compared with those in the control groups. These results indicated that HPEI nanogels delivering FILIP1LΔC103-p might be of value in the treatment against human ovarian cancer.