Antitumor activity of recombinant RGD-IFN-α2a-core fusion protein in vitro

Wen, Zhengwei; Jia, Qunying; Kang, Xiaojuan; Lou, Yongliang; Lilin, Zou; Yang, Jifeng; Jimin, Gao; Han, Liping; Li, Xiang

doi:10.1097/cad.0000000000000421

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…Alpha(v) beta (3) (αvβ3) is an important integrin. Previous studies revealed that αvβ3 is specifically overexpressed in activated endothelial cells and tumor cells but is not expressed or is rarely expressed in the vast majority of mature endothelial cells and normal cells [37,38]. Thus, the integrin αvβ3 could become a promising target for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

Huang

Liu

Feng³

et al. 2021

BMC Cancer

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Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

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Section: Introductionmentioning

confidence: 99%

RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

Huang

Liu

Feng³

et al. 2021

BMC Cancer

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“…It has been reported in the literature that the peptides and proteins containing RGD motifs, either in linear or cyclic form, recognize α v β 3 integrins and that this recognition can be used to target drugs to tumor cells [61]. Different cell lines express varying integrin proteins at different extents while cancer cells usually overexpress them [62][63][64][65]. Lung cancer cells are among the cancer cells overexpressing α v β 3 integrin receptors [62,65].…”

Section: Resultsmentioning

confidence: 99%

“…Different cell lines express varying integrin proteins at different extents while cancer cells usually overexpress them [62][63][64][65]. Lung cancer cells are among the cancer cells overexpressing α v β 3 integrin receptors [62,65]. Accordingly, we have utilized A549 (human lung adenocarcinoma epithelial) cell line as a model cell line overexpressing RGD-binding integrin receptors along with human bronchial epithelium BEAS-2B cells [63][64][65].…”

Section: Resultsmentioning

confidence: 99%

Efficient synthesis of cRGD functionalized polymers as building blocks of targeted drug delivery systems

Thankappan

Zelçak

Taykoz

et al. 2018

European Polymer Journal

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Synthetic peptides with cyclic arginine-glycine-aspartate motif (cRGD) play an important role in cell recognition and cell adhesion. cRGD-decorated soluble polymers and polymeric nanoparticles have been increasingly used for cell-specific delivery of antitumor drugs. While the significance of cRGD modification for tumor cell-specific targeting of polymeric carriers is well-accepted, straightforward procedures ensuring the fidelity of cRGD modification of polymeric systems are still lacking. Herein, we have reported an in-situ polymerization approach for synthesis of cRGD-end-functionalized well-defined polymers as potential building blocks of targeted drug delivery systems. A new cRGD peptide functionalized RAFT agent was synthesized as confirmed by MALDI-TOF and 1 H NMR spectroscopy. The ability of this RAFT agent to control polymerizations was then tested using two different monomers oligoethyleneglycol acrylate and t-butyl methacrylate. The RAFT-controlled character of polymerizations and the living characteristic of the synthesized polymers were investigated through a series of kinetic experiments. The cytotoxicity and targeting capability of cRGD-functionalized OEGA polymers were investigated using cell lines expressing α v β 3 integrins at varying extents.

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“…Recombinant proapoptotic proteins are an emerging class of cytotoxic biopharmaceuticals with high potential as anticancer agents and as alternatives to conventional small molecule drugs [12,[17][18][19][20]. Apoptosis is a programmed cell death mechanism that is crucial for maintaining tissue homeostasis in multicellular organisms by balancing cell proliferation and cell death [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug

et al. 2021

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The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.

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Antitumor activity of recombinant RGD-IFN-α2a-core fusion protein in vitro

Cited by 8 publications

References 21 publications

RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

Efficient synthesis of cRGD functionalized polymers as building blocks of targeted drug delivery systems

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug

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