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Inhibition of Hif-1Α/Ep4 Axis by Hyaluronate-Trimethyl Chitosan-Spion Nanoparticles Markedly Suppresses the Growth and Development of Cancer Cells Publisher Pubmed



Karpisheh V1, 2 ; Fakkari Afjadi J3 ; Nabi Afjadi M4 ; Haeri MS1 ; Abdpoor Sough TS2 ; Heydarzadeh Asl S2 ; Edalati M5 ; Atyabi F6 ; Masjedi A2 ; Hajizadeh F7 ; Izadi S8 ; Mirzazadeh Tekie FS6 ; Hajiramezanali M9 ; Sojoodi M10 Show All Authors
Authors
  1. Karpisheh V1, 2
  2. Fakkari Afjadi J3
  3. Nabi Afjadi M4
  4. Haeri MS1
  5. Abdpoor Sough TS2
  6. Heydarzadeh Asl S2
  7. Edalati M5
  8. Atyabi F6
  9. Masjedi A2
  10. Hajizadeh F7
  11. Izadi S8
  12. Mirzazadeh Tekie FS6
  13. Hajiramezanali M9
  14. Sojoodi M10
  15. Jadidiniaragh F2, 11

Source: International Journal of Biological Macromolecules Published:2021


Abstract

Increased expression of Hypoxia-inducible factor-1α (HIF-1α) in the tumor microenvironment, mainly due to tumor growth, plays a major role in the growth of cancer. Tumor cells induce the expression of cyclooxygenase 2 (COX2) and its product, prostaglandin E2 (PGE2), through overexpression of HIF-1α. It has been shown that ligation of PGE2 with its receptor, EP4, robustly promotes cancer progression. HIF-1α/COX2/PGE2/EP4 signaling pathways appear to play an important role in tumor growth. Therefore, we decided to block the expansion of cancer cells by blocking the initiator (HIF-1α) and end (EP4) of this pathway. In this study, we used hyaluronate (HA), and trimethyl chitosan (TMC) recoated superparamagnetic iron oxide nanoparticles (SPIONs) loaded with HIF-1α-silencing siRNA and the EP4 antagonist (E7046) to treat cancer cells and assessed the effect of combination therapy on cancer progression. The results showed that optimum physicochemical characteristics of NPs (size 126.9 nm, zeta potential 27 mV, PDI < 0.2) and linkage of HA with CD44 molecules overexpressed on cancer cells could deliver siRNAs to cancer cells and significantly suppress the HIF-1α in them. Combination therapy of cancer cells by using HIF-1α siRNA-loaded SPION-TMC-HA NPs and E7046 also prevent proliferation, migration, invasion, angiogenesis, and colony formation of the cancer cells, remarkably. © 2020
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