C-type natriuretic peptide in combination with sildenafil attenuates proliferation of rhabdomyosarcoma cells

Cancer Medicine
Masahiro ZenitaniKenji Kangawa

Abstract

Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma in children. Because of several complications associated with intensive multimodal therapies, including growth disturbance and secondary cancer, novel therapies with less toxicity are urgently needed. C-type natriuretic peptide (CNP), an endogenous peptide secreted by endothelial cells, exerts antiproliferative effects in multiple types of mesenchymal cells. Therefore, we investigated whether CNP attenuates proliferation of RMS cells. We examined RMS patient samples and RMS cell lines. All RMS clinical samples expressed higher levels of guanylyl cyclase B (GC-B), the specific receptor for CNP, than RMS cell lines. GC-B expression in RMS cells decreased with the number of passages in vitro. Therefore, GC-B stable expression lines were established to mimic clinical samples. CNP increased cyclic guanosine monophosphate (cGMP) levels in RMS cells in a dose-dependent manner, demonstrating the biological activity of CNP. However, because cGMP is quickly degraded by phosphodiesterases (PDEs), the selective PDE5 inhibitor sildenafil was added to inhibit its degradation. In vitro, CNP, and sildenafil synergistically inhibited proliferation of...Continue Reading

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Citations

Jan 20, 2017·Cancer Chemotherapy and Pharmacology·Masahiro ZenitaniKenji Kangawa
Oct 11, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Letizia MezzasomaIlaria Bellezza
Dec 13, 2017·Oncotarget·Ines BaroneStefania Catalano
Jul 9, 2021·Biomedical Journal·Mengjiao XuGeng Yang

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Methods Mentioned

BETA
PCR
xenograft
xenografts

Software Mentioned

CellSens Dimension
GraphPad Prism
GraphPad

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