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Codelivery of Stat3 Sirna and Bv6 by Carboxymethyl Dextran Trimethyl Chitosan Nanoparticles Suppresses Cancer Cell Progression Publisher Pubmed



Nikkhoo A1, 2 ; Rostami N1 ; Farhadi S3 ; Esmaily M4 ; Moghadaszadeh Ardebili S1 ; Atyabi F5 ; Baghaei M5 ; Haghnavaz N6 ; Yousefi M7 ; Aliparasti MR1 ; Ghalamfarsa G8 ; Mohammadi H9 ; Sojoodi M10 ; Jadidiniaragh F1, 11
Authors
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Authors Affiliations
  1. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  8. 8. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  9. 9. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  10. 10. Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, United States
  11. 11. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: International Journal of Pharmaceutics Published:2020


Abstract

High expression of inhibitor of apoptosis (IAP) molecules in cancer cells promotes cancer cell chemoresistance. Use of BV6, a well-known IAP inhibitor, along with inhibition of signal transducer and activator of transcription 3 (STAT3), which is an important factor in the survival of tumor cells, and NIK as a mediator of BV6 unpredicted side effects, can induce effective apoptosis in tumor cells. The present study has investigated the combination therapy of cancer cells using Carboxymethyl Dextran-conjugated trimethyl chitosan (TMC-CMD) nanoparticles (NPs) loaded with NIK/STAT3-specific siRNA and BV6 to synergistically induce apoptosis in the breast, colorectal and melanoma cancer cell lines. Our results showed that in addition to enhanced pro-apoptotic effects, this combination therapy reduced proliferation, cell migration, colony formation, and angiogenesis, along with expression of factors including IL-10 and HIF in tumor cells. The results indicate the potential of this combination therapy for further investigation in animal models of cancer. © 2020 Elsevier B.V.
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