Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway

Xiaoyi Zhang,Yaonan Wang,Jinhuan Zhang,Shurui Zhao,Ming Zhao,Wenchao Liu,Shiqi Peng,Jianhui Wu

doi:10.1038/s41598-020-72824-8

Xiaoyi Zhang, Yaonan Wang + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-72824-8

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Journal: Scientific Reports	Publication Date: Sep 25, 2020
Citations: 2	License type: open-access

Affiliation: Capital Medical University

Abstract

The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. AFM (atomic force microscopy) imaged that RGDV-gemcitabine was able to adhere onto the surface of serum-starved A549 cells, to block the extending of the pseudopodia. Thereby RGDV-gemcitabine was able to inhibit the invasion, migration and adhesion of serum-starved A549 cells in vitro. On C57BL/6 mouse model RGDV-gemcitabine dose dependently inhibited the metastasis of planted tumor towards the lung and the minimal dose was 0.084 µmol/kg/3 days. The decrease of serum TNF-α (tumor necrosis factor), IL-8 (interleukin-8), MMP-2 (matrix metalloprotein-2) and MMP-9 (matrix metalloprotein-9) of the treated C57BL/6 mice was correlated with the action pathway of RGDV-gemcitabine inhibiting the metastasis of the planted tumor towards lung.

Highlights

The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis
To enhance the efficacy of treating pancreatic cancer gemcitabine is combined with oxaliplatin, irinotecan, miR-345, nab-paclitaxel, RT11-i anti-body, metformin, ginkgolide B and m elatonin[7,8,9,10,11,12,13]
To upgrade the efficacy of treating osteosarcoma, advanced urothelial cancer, metastatic urothelial cancer, bladder cancer, hepatocellular carcinoma and urothelial bladder cancer gemcitabine is combined with licoricidin, taxanes, triptolide, chlorambucil and lentinan[22,23,24,25,26]

Summary

Introduction

The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. Thereby RGDV-gemcitabine was able to inhibit the invasion, migration and adhesion of serum-starved A549 cells in vitro. On C57BL/6 mouse model RGDV-gemcitabine dose dependently inhibited the metastasis of planted tumor towards the lung and the minimal dose was 0.084 μmol/kg/3 days. The decrease of serum TNF-α (tumor necrosis factor), IL-8 (interleukin-8), MMP-2 (matrix metalloprotein-2) and MMP-9 (matrix metalloprotein-9) of the treated C57BL/6 mice was correlated with the action pathway of RGDVgemcitabine inhibiting the metastasis of the planted tumor towards lung. To confirm this hypothesis the in vitro and in vivo actions of RGDV-gemcitabine on tumor metastasis and tumor growth were evaluated, and the possible mechanism was discussed

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