Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic

Shanker, Manish; Jin, Jiankang; Branch, Cynthia D.; Miyamoto, Shinya; Grimm, Elizabeth A.; Roth, Jack A.; Ramesh, Rajagopal

doi:10.1155/2011/465845

Cited by 20 publications

(13 citation statements)

References 62 publications

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“…The remaining 5 mice per treatment group were used for counting extrapulmonary lung nodules as previously described [25, 33, 35]. Briefly, 10 ml of Bouin’s fluid was intratracheally injected into the lungs of sacrificed mice.…”

Section: Methodsmentioning

confidence: 99%

Tumor-targeted Nanoparticle Delivery of HuR siRNA Inhibits Lung Tumor Growth In Vitro and In Vivo By Disrupting the Oncogenic Activity of the RNA-binding Protein HuR

Muralidharan

Babu

Amreddy

et al. 2017

Molecular Cancer Therapeutics

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Selective downregulation of the human antigen R (HuR) protein by siRNA may provide a powerful approach for treating lung cancer. To this end, we investigated the efficacy of transferrin receptor-targeted liposomal nanoparticle-based HuR siRNA (HuR-TfNP) therapy and compared to control siRNA (C)-TfNP therapy both, in vitro and in vivo using lung cancer models. In vitro studies showed HuR-TfNP but not C-TfNP efficiently downregulated HuR and HuR-regulated proteins in A549, and HCC827 lung cancer cells resulting in reduced cell viability, inhibition of cell migration and invasion, and induction of G1 cell-cycle arrest culminating in apoptosis. However, HuR-TfNP activity in normal MRC-9 lung fibroblasts was negligible. In vivo biodistribution study demonstrated that fluorescently labeled HuR-siRNA or ICG dye loaded TfNP localized in tumor tissues. Efficacy studies showed intratumoral or intravenous administration of HuR-TfNP significantly inhibited A549 (>55% inhibition) and HCC827 (>45% inhibition) subcutaneous tumor growth compared to C-TfNP. Furthermore, HuR-TfNP treatment reduced HuR, Ki67, and CD31 expression and increased caspase-9 and PARP cleavage and TUNEL positive staining indicative of apoptotic cell death in tumor tissues compared to C-TfNP treatment. The antitumor activity of HuR-TfNP was also observed in an A549-luc lung metastatic model, as significantly fewer tumor nodules (9.5±3.1; p<0.001; 88% inhibition) were observed in HuR-TfNP-treated group compared with the C-TfNP-treated group (77.7±20.1). Significant reduction in HuR, Ki67, and CD31 expression was also observed in the tumor tissues of HuR-TfNP-treatment compared to C-TfNP treatment. Our findings highlight HuR-TfNP as a promising nano-therapeutic system for lung cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Tumor-targeted Nanoparticle Delivery of HuR siRNA Inhibits Lung Tumor Growth In Vitro and In Vivo By Disrupting the Oncogenic Activity of the RNA-binding Protein HuR

Muralidharan

Babu

Amreddy

et al. 2017

Molecular Cancer Therapeutics

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“…It has been proved that TSGs contribute to drug resistance in several types of solid tumors. For example, TSGs including E1A, p53, Fhit, IL-24, Fus1 and BiKDD are associated with drug resistance in ovarian, lung and pancreatic cancer, and these genes are potential genes for gene therapy (10). In this study, on the basis of published reports, 15 TSGs which contributed to drug resistance in ovarian cancer were reviewed to provide an overview of the relationship of TSGs with ovarian cancer drug resistance; meanwhile, protein interactions and bio-association analysis were performed to demonstrate the associations of these TSGs and to mine the potential drug resistance-related genes which are closely related to the 15 TSGs.…”

Section: Tumor Suppressor Genes Associated With Drug Resistance In Ovmentioning

confidence: 99%

Tumor suppressor genes associated with drug resistance in ovarian cancer (Review)

Yin

Liu

et al. 2013

Oncology Reports

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Ovarian cancer is a fatal gynecological cancer and a major cause of cancer-related mortality worldwide. The main limitation to a successful treatment for ovarian cancer is the development of drug resistance to combined chemotherapy. Tumor suppressor genes (TSGs) are wild-type alleles of genes which play regulatory roles in diverse cellular activities, and whose loss of function contributes to the development of cancer. It has been demonstrated that TSGs contribute to drug resistance in several types of solid tumors. However, an overview of the contribution of TSGs to drug resistance in ovarian cancer has not previously been reported. In this study, 15 TSGs responding to drug resistance in ovarian cancer were reviewed to determine the relationship of TSGs with ovarian cancer drug resistance. Furthermore, gene/protein-interaction and bio-association analysis were performed to demonstrate the associations of these TSGs and to mine the potential drug resistance-related genes in ovarian cancer. We observed that the 15 TSGs had close interactions with each other, suggesting that they may contribute to drug resistance in ovarian cancer as a group. Five pathways/processes consisting of DNA damage, apoptosis, cell cycle, DNA binding and methylation may be the key ways with which TSGs participate in the regulation of drug resistance. In addition, ubiquitin C (UBC) and six additional TSGs including the adenomatous polyposis coli gene (APC), death associated protein kinase gene (DAPK), pleiomorphic adenoma gene-like 1 (PLAGL1), retinoblastoma susceptibility gene (RB1), a gene encoding an apoptosis-associated speck-like protein (PYCARD/ASC) and tumor protein 63 (TP63), which had close interactions with the 15 TSGs, are potential drug resistance-related genes in ovarian cancer.

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“…Previous studies have confirmed that the transfection of tumor suppressor genes can significantly reduce the growth and metastatic ability of breast cancer cells (5). Breast cancer suppressor candidate-1 (BCSC-1; also termed von Willebrand factor A domain containing 5A and LOH11CR2A) is a newly identified tumor suppressor gene localized at chromosome 11q23-q24.…”

Section: Introductionmentioning

confidence: 95%

BCSC-1 suppresses human breast cancer metastasis by inhibiting NF-κB signaling

Chen

Guo

et al. 2018

Int J Oncol

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Breast cancer suppressor candidate-1 (BCSC-1; also termed von Willebrand factor A domain containing 5A and LOH11CR2A) is a newly identified candidate tumor suppressor gene that has been implicated in several types of cancer in previous studies. However, there have been few reports about the association between BCSC-1 and human breast cancer in recent years. In the present study, the expression of BCSC-1 in breast cancer was determined by immunohistochemistry (IHC) staining of tissue microarrays and clinical tissue specimens. Subsequently, BCSC-1 gene expression was evaluated in different breast cancer cell lines by quantitative polymerase chain reaction and the MDA-MB-231 cell line was selected for further use in subsequent experiments, due to its low BCSC-1 expression. An MDA-MB-231 cell line with stable overexpression of BCSC-1 was established through transfection with plasmid containing the BCSC-1 gene, and then screening for G418 resistance. Wound-healing, migration and invasion assays were conducted to detect the effect of BCSC-1 on MDA-MB-231 cells. Furthermore, changes in matrix metalloproteinases (MMPs), osteopontin (OPN) and the nuclear factor-κB (NF-κB) pathway were detected in the current study. Additionally, stable silencing of BCSC-1 expression in MCF-7 cells was performed using a lentivirus. The results of IHC indicated that BCSC-1 is expressed at low levels in breast cancer tissues compared with in normal breast tissue. Results of the wound healing, migration and invasion assays demonstrated that BCSC-1 overexpression reduced the metastasis ability of MDA-MB-231 cells in vitro. Further research confirmed that the BCSC-1 overexpression reduced the expression levels of MMP7, MMP9 and OPN, and the phosphorylation of NF-κB p65. Furthermore, inhibition of BCSC-1 via lentivirus-mediated RNA interference revealed that the downregulation of BCSC-1 increased the invasive ability of MCF-7 cells. In summary, the results demonstrated that BCSC-1 is expressed at low levels in breast cancer tissues, and that it can suppress human breast cancer cell migration and invasion, potentially altering the expression of MMP7, MMP9, OPN, and the activity of the NF-κB pathway. Therefore, BCSC-1 may be useful as a biomarker for the treatment of breast cancer in the future.

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Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic

Cited by 20 publications

References 62 publications

Tumor-targeted Nanoparticle Delivery of HuR siRNA Inhibits Lung Tumor Growth In Vitro and In Vivo By Disrupting the Oncogenic Activity of the RNA-binding Protein HuR

Tumor-targeted Nanoparticle Delivery of HuR siRNA Inhibits Lung Tumor Growth In Vitro and In Vivo By Disrupting the Oncogenic Activity of the RNA-binding Protein HuR

Tumor suppressor genes associated with drug resistance in ovarian cancer (Review)

BCSC-1 suppresses human breast cancer metastasis by inhibiting NF-κB signaling

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