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Silencing of P68 and Stat3 Synergistically Diminishes Cancer Progression Publisher Pubmed



Hashemi V1, 2 ; Ahmadi A3 ; Malakotikhah F1 ; Chaleshtari MG1 ; Baghi Moornani M1 ; Masjedi A1 ; Sojoodi M4 ; Atyabi F5 ; Nikkhoo A1 ; Rostami N1 ; Baradaran B6 ; Azizi G7 ; Yousefi B8 ; Ghalamfarsa G9 Show All Authors
Authors
  1. Hashemi V1, 2
  2. Ahmadi A3
  3. Malakotikhah F1
  4. Chaleshtari MG1
  5. Baghi Moornani M1
  6. Masjedi A1
  7. Sojoodi M4
  8. Atyabi F5
  9. Nikkhoo A1
  10. Rostami N1
  11. Baradaran B6
  12. Azizi G7
  13. Yousefi B8
  14. Ghalamfarsa G9
  15. Jadidiniaragh F6, 10
Show Affiliations
Authors Affiliations
  1. 1. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Department of Chemical and Materials Engineering, The University of Alabama in Huntsville, 35899, AL, United States
  4. 4. Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, United States
  5. 5. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1714614411, Iran
  6. 6. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  8. 8. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  9. 9. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  10. 10. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Life Sciences Published:2020


Abstract

Aims: Since several factors are involved in the tumorigenesis process, targeting only one factor most probably cannot overwhelm cancer progression. Therefore, it seems that combination therapy through targeting more than one cancer-related factor may lead to cancer control. The expression and function of p68 (DDX5; DEAD-Box Helicase 5) are dysregulated in various cancers. P68 is also a co-activator of many oncogenic transcription factors such as the signal transducer and activator of transcription-3 (STAT3), which contributes to cancer progression. This close connection between p68 and STAT3 plays an important role in the growth and development of cancer. Materials and methods: We decided to suppress the p68/STAT3 axis in various cancer cells by using Polyethylene glycol-trimethyl Chitosan-Hyaluronic acid (PEG-TMC-HA) nanoparticles (NPs) loaded with siRNA molecules. We assessed the impact of this combination therapy on apoptosis, proliferation, angiogenesis, and tumor growth, both in vitro and in vivo. Key findings: The results showed that siRNA-loaded NPs notably suppressed the expression of p68/STAT3 axis in cancer cells, which was associated with blockade of tumor growth, colony formation, angiogenesis, and cancer cell migration. In addition to apoptosis induction, this combined therapy also reduced the expression of several tumor-promoting factors including Fibroblast growth factors (FGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), matrix metallopeptidases-2 (MMP-2), MMP-9, hypoxia-inducible factor-(HIF-1α), interleukin-6 (IL-6), IL-33, Bcl-x, vimentin, and snail. Significance: These findings indicate the potential of this nano-based anti-cancer therapeutic strategy for efficient cancer therapy which should be further investigated in future studies. © 2020 Elsevier Inc.
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