Codelivery of STAT3 siRNA and BV6 by carboxymethyl dextran trimethyl chitosan nanoparticles suppresses cancer cell
Afshin Nikkhoo1, Narges Rostami2, Shohreh Farhadi3
1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
Insights
This study combined nanoparticles with BV6 to target cancer cell survival pathways. The novel combination therapy effectively induced apoptosis and reduced tumor growth in breast, colorectal, and melanoma cancer cells.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- High expression of inhibitor of apoptosis (IAP) molecules contributes to cancer chemoresistance.
- Signal transducer and activator of transcription 3 (STAT3) and NIK are crucial for tumor cell survival and BV6 side effects.
Purpose of the Study:
- To investigate the synergistic effect of Carboxymethyl Dextran-conjugated trimethyl chitosan (TMC-CMD) nanoparticles loaded with NIK/STAT3-specific siRNA and BV6.
- To evaluate this combination therapy's efficacy in inducing apoptosis in breast, colorectal, and melanoma cancer cell lines.
Main Methods:
- Utilized TMC-CMD nanoparticles to deliver NIK/STAT3-specific siRNA and BV6.
- Assessed the combination therapy's impact on apoptosis, proliferation, migration, colony formation, and angiogenesis.
- Measured the expression of IL-10 and HIF.
Main Results:
- The combination therapy demonstrated enhanced pro-apoptotic effects.
- Significant reduction in cancer cell proliferation, migration, and colony formation was observed.
- Inhibition of angiogenesis and downregulation of IL-10 and HIF expression were noted.
Conclusions:
- The developed nanoparticle-based combination therapy shows significant potential for synergistic cancer treatment.
- Further investigation in preclinical cancer models is warranted to explore its therapeutic application.
