Sonic hedgehog-glioma associated oncogene homolog 1 signaling enhances drug resistance in CD44+/Musashi-1+ gastric cancer stem cells

2015 ◽  
Vol 369 (1) ◽  
pp. 124-133 ◽  
Author(s):  
Min Xu ◽  
Aihua Gong ◽  
Hongqiong Yang ◽  
Suraj K. George ◽  
Zhijun Jiao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Sonic Hedgehog ◽  
Gastric Cancer Stem Cells

Sulforaphane inhibits gastric cancer stem cells via suppressing sonic hedgehog pathway

2019 ◽  
Vol 70 (5) ◽  
pp. 570-578 ◽  
Author(s):  
Miaomiao Ge ◽  
Lu Zhang ◽  
Lina Cao ◽  
Chunfeng Xie ◽  
Xiaoting Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Pathway ◽  
Sonic Hedgehog Pathway ◽  
Gastric Cancer Stem Cells

scholarly journals Apatinib Suppresses Gastric Cancer Stem Cells Properties by Inhibiting the Sonic Hedgehog Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Wanshuang Cao ◽  
Yuan Li ◽  
Hongliang Sun ◽  
Chenying Yang ◽  
Jianyun Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Advanced Gastric Cancer ◽  
Sonic Hedgehog ◽  
Xenograft Model ◽  
Inhibitory Effects ◽  
Antitumor Effects ◽  
Shh Pathway ◽  
Gastric Cancer Stem Cells

The presence of gastric cancer stem cells (GCSCs) marks the onset of gastric carcinoma. The sonic hedgehog (SHH) pathway plays a vital role in the maintenance of GCSC characteristics. Apatinib has been approved in China for advanced gastric cancer (GC) treatment. However, whether apatinib can target GCSCs and affect the SHH pathway remains unclear. The present study aimed to investigate the underlying mechanism of apatinib’s antitumor effects on GC. The expression levels of GCSC markers and number of CD133+ cells were significantly elevated in the sphere-forming cells. Apatinib effectively suppressed GCSC traits by inhibiting tumorsphere formation and cell proliferation, suppressing GCSC markers expression and CD133+ cell number, and inducing apoptosis. Apatinib downregulated the activation of the SHH pathway; while upregulation of the SHH pathway attenuated the inhibitory effects of apatinib on GCSCs. Moreover, apatinib treatment significantly delayed tumor growth and inhibited GCSC characteristics in the xenograft model. Our data suggested that apatinib exhibited inhibitory effects on GCSCs by suppressing SHH pathway both in vitro and in vivo, thus providing new insights into the therapeutic application of apatinib in GCSC suppression and advanced gastric cancer treatment.

scholarly journals Apatinib Suppresses Gastric Cancer Stem Cells Properties by Inhibiting Sonic Hedgehog Pathway

2020 ◽  
Author(s):  
Wanshuang Cao ◽  
Yuan Li ◽  
Hongliang Sun ◽  
Jianyun Zhu ◽  
Chunfeng Xie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Cancer Stem Cells ◽  
Advanced Gastric Cancer ◽  
Sonic Hedgehog ◽  
Xenograft Model ◽  
Inhibitory Effects ◽  
Shh Pathway ◽  
Gastric Cancer Stem Cells

Abstract Background Gastric cancer stem cells (GCSCs) are considered as the basis of gastric carcinoma onset. Sonic Hedgehog (SHH) pathway plays a crucial role in maintaining GCSCs characteristics. Apatinib, a highly selective vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, has been approved in China for the treatment of advanced gastric cancer after the failure of second-line therapy. To data, the effects of apatinib on GCSCs and the underlying mechanisms have not been elucidated yet.Methods Tumorsphere formation assay was used to enrich GCSCs from BGC-823 and SGC-7901 cells and the number of CD133-positive cells was examined by flow cytometry. Western blotting, immunofluorescence and immunohistochemistry assays were used to determine protein expression. Cell proliferation and apoptosis of GCSCs after apatinib treatment were evaluated by CCK8, colony formation, flow cytometry and Hoechst 33258 assays. Transient transfection assay was used to upregulate Gli1 expression in GCSCs. Nude mouse xenograft was used to investigate the suppressive effects of apatinib in vivo. Results We revealed that the levels of GCSCs markers and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that apatinib efficiently abolished GCSCs traits, as manifested by inhibition of tumorsphere formation, decreased expression of GCSCs markers, reduced number of CD133-positive cells, drug resistance protein suppression as well as proliferation inhibition and apoptosis induction. Furthermore, we found that apatinib downregulated the activation of SHH pathway, while upregulation of SHH pathway attenuated the inhibitory effects of apatinib on GCSCs. Furthermore, apatinib treatment significantly delayed tumor growth and inhibited GCSCs characteristics in xenograft model. Conclusions Taken together, our data suggested that apatinib exhibited its inhibitory effects on GCSCs via suppression of SHH pathway. These findings could provide new insights into the therapeutic application of apatinib in GCSCs suppression and advanced gastric cancer treatment.

Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

2020 ◽  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Cancer Stem Cells ◽  
Histopathological Examination ◽  
Physiological Saline ◽  
Rrna Gene ◽  
Peptic Ulcers ◽  
Gastric Cancer Stem Cells ◽  
H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

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