Piezo1 Is as a Novel Trefoil Factor Family 1 Binding Protein that Promotes Gastric Cancer Cell Mobility In Vitro

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

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Blocking TGF-β1 by P17 peptides attenuates gastric cancer cell induced peritoneal fibrosis and prevents peritoneal dissemination in vitro and in vivo

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.01.039 ◽

2017 ◽

Vol 88 ◽

pp. 27-33 ◽

Cited By ~ 6

Author(s):

Zhi-Dong Lv ◽

Wei-Jun Zhao ◽

Li-Ying Jin ◽

Wen-Juan Wang ◽

Qian Dong ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Peritoneal Dissemination ◽

Peritoneal Fibrosis ◽

Tgf Β1

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Retracted: si-RNA-Mediated Knockdown of PDLIM5 Suppresses Gastric Cancer Cell Proliferation in Vitro

Chemical Biology & Drug Design ◽

10.1111/cbdd.12428 ◽

2014 ◽

Vol 85 (4) ◽

pp. 447-453 ◽

Cited By ~ 10

Author(s):

Yanliang Li ◽

Yongsheng Gao ◽

Yue Xu ◽

Xianjun Sun ◽

Xilin Song ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Cancer Cell Proliferation ◽

Gastric Cancer Cell Proliferation ◽

Si Rna ◽

Proliferation In Vitro

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Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20194826 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4826 ◽

Cited By ~ 5

Author(s):

Rachel Sexton ◽

Zaid Mahdi ◽

Rahman Chaudhury ◽

Rafic Beydoun ◽

Amro Aboukameel ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Nuclear Export ◽

Gastric Cancer Cell ◽

Clinical Investigation ◽

Chromosome Region ◽

Specific Inhibitor ◽

Anti Tumor Activity

Gastric cancer remains an unmet clinical problem in urgent need of newer and effective treatments. Here we show that the nuclear export protein, Exportin 1 (XPO1, chromosome region maintenance 1 or CRM1), is a promising molecular target in gastric cancer. We demonstrate significant overexpression of XPO1 in a cohort of histologically diverse gastric cancer patients with primary and metastatic disease. XPO1 RNA interference suppressed gastric cancer cell growth. Anti-tumor activity was observed with specific inhibitor of nuclear export (SINE) compounds (selinexor/XPOVIO), second-generation compound KPT-8602/eltanexor, KPT-185 and +ve control Leptomycin B in three distinct gastric cancer cell lines. SINE compounds inhibited gastric cancer cell proliferation, disrupted spheroid formation, induced apoptosis and halted cell cycle progression at the G1/S phase. Anti-tumor activity was concurrent with nuclear retention of tumor suppressor proteins and inhibition of colony formation. In combination studies, SINE compounds enhanced the efficacy of nab-paclitaxel in vitro and in vivo. More significantly, using non-coding RNA sequencing studies, we demonstrate for the first time that SINE compounds can alter the expression of non-coding RNAs (microRNAs and piwiRNAs). SINE treatment caused statistically significant downregulation of oncogenic miR-33b-3p in two distinct cell lines. These studies demonstrate the therapeutic significance of XPO1 in gastric cancer that warrants further clinical investigation.

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