A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD

Zhang, Qing; Zhang, Yang; Li, Ké; Li, Ang; Li, Huizhong; Zheng, Junnian

doi:10.1371/journal.pone.0129865

Cited by 27 publications

(28 citation statements)

References 48 publications

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“…Treatment comprising a combination of GEM and iRGD was applied, which inhibited the growth of tumors, which were not sensitive to the same dose of GEM alone. Apoptotic cells in the tumor tissues were detected using a TUNEL assay and the statistical analysis revealed that the highest apoptotic index was for the groups treated with the GEM/iRGD combination (38).…”

Section: Irgd For Tumor Diagnosis and Treatmentmentioning

confidence: 99%

iRGD as a tumor-penetrating peptide for cancer therapy

Yin

Zhang

Yang

et al. 2017

Molecular Medicine Reports

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As a tumor-targeting and ‑penetrating peptide, iRGD binds to αv integrins and neuropilin‑1 receptors, which are expressed at high levels on tumor cells and the surfaces of vasculature. Subsequently, iRGD penetrates deep into the tumor parenchyma with antitumor drugs, imaging agents, immune modulators and biological products. These substances are either chemically linked to the peptide or co‑injected with the peptide. The iRGD peptide can be readily synthesized, exhibits significantly improved penetration, compared with traditional peptides, and can effectively inhibit tumor metastasis. Therefore, the peptide is now used widely for the diagnosis and treatment of cancer. However, whether the peptide is able to promote the entry of drugs into non‑targeted cells remains to be fully elucidated. In this review, an overview of iRGD is presented, focusing on its identification, mechanism of action and previous studies on its roles in various types of cancer. Studies in previous years have demonstrated the potential of the iRGD protein for tumors diagnosis and targeted treatment, which warrants further investigation.

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Section: Irgd For Tumor Diagnosis and Treatmentmentioning

confidence: 99%

iRGD as a tumor-penetrating peptide for cancer therapy

Yin

Zhang

Yang

et al. 2017

Molecular Medicine Reports

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“…In a hepatocarcinoma xenograft model, utilizing the same mouse strain as Sugahara et al, Schmithals et al reported that co-administration of iRGD enhanced the penetration of DOX into tumor tissue as well as reduced tumor size as compared to DOX alone (Schmithals et al, 2015; Sugahara et al, 2010). Utilizing a different chemotherapeutic, Zhang et al reported that in an A549 xenograft model of non-small cell lung cancer, co-administration of iRGD along with gemcitabine lead to increased penetrance of drug to the tumor and decreased tumor volume over the treatment period of 30 days (Zhang et al, 2015). Finally, Lao et al reported that a thymosin alpha 1-iRGD conjugated form increased apoptosis of MCF-7 cells and decreased tumor volume over an 11 day treatment period when compared to thymosin alpha 1 alone (Lao et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Replication Study: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs

Mantis

Kandela

Aird

2017

eLife

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In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper “Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs“ (Sugahara et al., 2010). Here we report the results of those experiments. We found that coadministration with iRGD peptide did not have an impact on permeability of the chemotherapeutic agent doxorubicin (DOX) in a xenograft model of prostate cancer, whereas the original study reported that it increased the penetrance of this cancer drug (Figure 2B; Sugahara et al., 2010). Further, in mice bearing orthotopic 22Rv1 human prostate tumors, we did not find a statistically significant difference in tumor weight for mice treated with DOX and iRGD compared to DOX alone, whereas the original study reported a decrease in tumor weight when DOX was coadministered with iRGD (Figure 2C; Sugahara et al., 2010). In addition, we did not find a statistically significant difference in TUNEL staining in tumor tissue between mice treated with DOX and iRGD compared to DOX alone, while the original study reported an increase in TUNEL positive staining with iRGD coadministration (Figure 2D; Sugahara et al., 2010). Similar to the original study (Supplemental Figure 9A; Sugahara et al., 2010), we did not observe an impact on mouse body weight with DOX and iRGD treatment. Finally, we report meta-analyses for each result.DOI: http://dx.doi.org/10.7554/eLife.17584.001

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“…Lung cancer is the most common cause of mortality in the world with an increasing incidence . The diagnosis is often made until reaching advanced‐stage, thus probably resulting in metastasis and a low survival rate of patients . Metastasis is a multistep process including local invasion, intravasation, extravasation, and colonization by which tumor cells disseminate from their primary site and form secondary tumors at a distant site .…”

Section: Introductionmentioning

confidence: 99%

Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-κB signaling pathway

et al. 2016

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Inflammatory microenvironment created by immune cells is favorable for tumor metastasis. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in inflammatory microenvironment. In this study, we sought to investigate the effects of Icariside II, a flavonol glycoside isolated from Epimedium koreanum Nakai, on A549 and H1299 cells migration in inflammatory microenvironment. At non-cytotoxic concentrations, Icariside II could inhibit invasion and EMT of A549 and H1299 cells induced by LPS-stimulated-THP-1 medium or by pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Exposure to Icariside II resulted in the increment of E-cadherin, accompanied with decrement of N-cadherin, vimentin, Slug, and Snail in A549 and H1299 cells stimulated by TNF1α. Furthermore, Icariside II suppressed TNF-α-triggered nuclear translocation of NF-κB and phosphorylation of IκBα, and repressed the DNA-binding activity of NF-κB. Further data demonstrated that Akt/GSK-3β, other than MAPK signaling pathway was taking a part in the inhibitory potential of Icariside II on NF-κB activation. Importantly, Icariside II also impeded lung metastasis of A549 cells and EMT in nude mice. In conclusion, Icariside II might prohibit invasion through inactivating Akt/NF-κB pathway. © 2016 Wiley Periodicals, Inc.

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A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD

Cited by 27 publications

References 48 publications

iRGD as a tumor-penetrating peptide for cancer therapy

iRGD as a tumor-penetrating peptide for cancer therapy

Replication Study: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs

Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-κB signaling pathway

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