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A Tumor-Specific Tissue-Penetrating Peptide Enhances the Efficacy of Chemotherapy Drugs in Gastric Cancer.


ABSTRACT:

Purpose

C-end rule (CendR) peptides are found to enhance the penetration of chemotherapeutic agents into tumor cells, while GX1 is a peptide that homes to gastric cancer (GC) vasculature. This study aimed to synthesize a novel peptide GX1-RPAKPAR (GXC) and to explore the effect of GXC on sensitizing GC cells to chemotherapeutic agents.

Materials and methods

Intracellular Adriamycin concentration analysis was applied to conform whether GXC peptide increases the penetration of chemotherapeutic agents into GC cells in vitro. The effect of GXC peptide on sensitizing GC cells to chemotherapeutics was validated by apoptosis assay and in vitro/vivo drug sensitivity assay. The specificity of GXC to GC tissue was validated by ex vivo fluorescence imaging.

Results

In vitro, administration of GXC significantly increased Adriamycin concentrations inside SGC-7901 cells, and enhanced the efficacy of chemotherapeutic agents by decreasing the IC?? value. In vivo, FITC-GXC specifically accumulated in GC tissue. Moreover, systemic co-injection with GXC peptide and Adriamycin statistically improved the therapeutic efficacy in SGC-7901 xenograft models, surprisingly, without obviously increasing side effects.

Conclusion

These results demonstrated that co-administration of the novel peptide GXC with chemotherapeutic agents may be a potential way to enhance the efficacy of anticancer drugs in GC treatment.

SUBMITTER: Jin Z 

PROVIDER: S-EPMC5990678 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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A Tumor-Specific Tissue-Penetrating Peptide Enhances the Efficacy of Chemotherapy Drugs in Gastric Cancer.

Jin Zhian Z   Wang Pujie P   Chen Jie J   He Li L   Xiao Lijia L   Yong Kaisen K   Deng Shenglin S   Zhou Lin L  

Yonsei medical journal 20180701 5


<h4>Purpose</h4>C-end rule (CendR) peptides are found to enhance the penetration of chemotherapeutic agents into tumor cells, while GX1 is a peptide that homes to gastric cancer (GC) vasculature. This study aimed to synthesize a novel peptide GX1-RPAKPAR (GXC) and to explore the effect of GXC on sensitizing GC cells to chemotherapeutic agents.<h4>Materials and methods</h4>Intracellular Adriamycin concentration analysis was applied to conform whether GXC peptide increases the penetration of chemo  ...[more]

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