Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes

Nanomedicine ◽  
2019 ◽  
Vol 14 (24) ◽  
pp. 3127-3142
Author(s):  
Mariarosa Mazza ◽  
Hassan Ahmad ◽  
Marilena Hadjidemetriou ◽  
Giulia Agliardi ◽  
Omar N. Pathmanaban ◽  
...  

Aim: To develop a nonviral tool for the delivery of siRNA to brain tumor cells using peptide nanofibers (PNFs). Materials & methods: Uptake of PNFs was evaluated by confocal microscopy and flow cytometry. Gene silencing was determined by RT-qPCR and cell invasion assay. Results: PNFs enter phagocytic (BV-2) and nonphagocytic (U-87 MG) cells via endocytosis and passive translocation. si PLK1 delivered using PNFs reduced the expression of polo-like kinase 1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, targeting MMP2 using PNF:si MMP2 reduced the invasion capacity of U-87 MG cells. We show that stereotactic intra-tumoral administration of PNF:si PLK1 significantly extends the survival of tumor bearing mice comparing with the untreated tumor bearing animals. Conclusion: Our results suggest that this nanomedicine-based RNA interference approach deserves further investigation as a potential brain tumor therapeutic tool.

Author(s):  
Yangyang Liu ◽  
Yonglu Li ◽  
Wen Chen ◽  
Xiang Ye ◽  
Ruoyi Jia ◽  
...  

Abstract: Tetrastigma hemsleyanum has been regarded as an anticancer food in China. However, its corresponding mechanisms remains unclear. Thus, in this study, the antitumor activity of flavones-rich fraction of root of Tetrastigma hemsleyanum (FRTH) was investigated in vitro and in vivo. The results indicated that FRTH could inhibit the proliferation and migration of HepG2 cells in vitro by PI3K/AKT pathway. FRTH could increase the ROS level and change the mitochondrial membrane potential (MMP) in HepG2 cells. In addition, FRTH treatment (300, 600 mg/kg BW) significantly suppressed tumor growth on HepG2 tumor-bearing nude mice. Besides, immunohistochemistry assays and western blotting revealed that FRTH enhanced the expression level of Bax/Bcl-2, cytochrome C, Caspase-3, caspase-9, Cleaved-caspase-3, and downregulated the expression level of CD31, ki67 and VEGF in HepG2 tumor-bearing mice. Our study suggests Tetrastigma hemsleyanum as a promising candidate medicine for liver cancer treatment.


2019 ◽  
Vol 20 (3) ◽  
pp. 545 ◽  
Author(s):  
Sergio Córdova-Rivas ◽  
Ixamail Fraire-Soto ◽  
Andrea Mercado-Casas Torres ◽  
Luis Servín-González ◽  
Angelica Granados-López ◽  
...  

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand’s expression and function is studied in cervical cancer. The 3p strand’s function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer.


2017 ◽  
Author(s):  
Serena Martinelli ◽  
Vanessa D'Antongiovanni ◽  
Susan Richter ◽  
Letizia Canu ◽  
Tonino Ercolino ◽  
...  

2020 ◽  
Author(s):  
Lungwani Muungo

ADP ribosylation factor GTPase-activating protein 3 (ARFGAP3) is a GTPase-activating protein that associates with the Golgiapparatus and regulates the vesicular trafficking pathway. In the present study, we examined the contribution of ARFGAP3 toprostate cancer cell biology. We showed that ARFGAP3 expression was induced by 100 nM of dihydrotestosterone (DHT) atboth the mRNA and protein levels in androgen-sensitive LNCaP cells. We generated stable transfectants of LNCaP cells withFLAG-tagged ARFGAP3 or a control empty vector and showed that ARFGAP3 overexpression promoted cell proliferation andmigration compared with control cells. We found that ARFGAP3 interacted with paxillin, a focal adhesion adaptor protein thatis important for cell mobility and migration. Small interfering RNA (siRNA)-mediated knockdown of ARFGAP3 showed thatARFGAP3 siRNA markedly reduced LNCaP cell growth. Androgen receptor (AR)-dependent transactivation activity on prostatespecificantigen (PSA) enhancer was synergistically promoted by exogenous ARFGAP3 and paxillin expression, as shown byluciferase assay in LNCaP cells. Thus, our results suggest that ARFGAP3 is a novel androgen-regulated gene that can promoteprostate cancer cell proliferation and migration in collaboration with paxillin.


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