Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer

Zhou,Wei; Tan,Wei; Huang,Xu; Yu,Hong  Gang

doi:10.3892/ol.2018.9039

Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer

Authors:
- Wei Zhou
- Wei Tan
- Xu Huang
- Hong Gang Yu
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Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: June 28, 2018 https://doi.org/10.3892/ol.2018.9039
Pages: 2805-2812
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Notch1, a transmembrane receptor that has a notable role in gastric cancer (GC) as an oncogene, has been reported to be involved in doxorubicin resistance. Thus, Notch1 is a potential therapeutic target for GC. In the present study, the protein levels of Notch1 intracellular domain (NICD; a marker of Notch1 activation) in human GC cell lines and tumor tissues was measured by western blotting. Next, the effects of Notch1 depletion in SGC7901 cells were evaluated. Finally, the efficacy of Notch1 small interfering RNA (siRNA) combined with doxorubicin therapy for GC was examined in vitro and in vivo. The results revealed that NICD levels were high in GC cells, and that the inhibition of NICD by transfection with Notch1 siRNA induced apoptosis and inhibited proliferation. Ectopic downregulation of Notch1 expression enhanced the sensitivity of GC tumors to doxorubicin, which suppressed the development of GC. These data demonstrated that Notch1 was a significant regulator of cell proliferation and apoptosis in GC. Thus, the combination of doxorubicin with Notch1 siRNA is a potential strategy for the treatment of GC.

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