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Silencing of p68 and STAT3 synergistically diminishes cancer progression
Vida Hashemi1, Armin Ahmadi2, Farinaz Malakotikhah3
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
Insights
This study developed a novel nanoparticle therapy to target the p68/STAT3 axis in cancer. The combination therapy effectively suppressed tumor growth, angiogenesis, and metastasis, showing promise for future cancer treatments.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Cancer progression involves multiple factors, necessitating combination therapies.
- The p68 (DDX5) protein and STAT3 signaling pathway are crucial in various cancers.
- p68 acts as a co-activator for oncogenic transcription factors like STAT3, promoting cancer development.
Purpose of the Study:
- To investigate the efficacy of a combination therapy targeting the p68/STAT3 axis in cancer cells.
- To develop a novel nano-drug delivery system for simultaneous suppression of p68 and STAT3.
- To evaluate the anti-cancer effects of this strategy in vitro and in vivo.
Main Methods:
- Utilized Polyethylene glycol-trimethyl Chitosan-Hyaluronic acid (PEG-TMC-HA) nanoparticles (NPs) loaded with siRNA.
- Administered NPs to various cancer cells to suppress the p68/STAT3 axis.
- Assessed effects on apoptosis, proliferation, angiogenesis, and tumor growth.
Main Results:
- siRNA-loaded NPs effectively suppressed p68/STAT3 expression in cancer cells.
- Therapy led to significant blockade of tumor growth, colony formation, angiogenesis, and migration.
- Reduced expression of key tumor-promoting factors including FGF, VEGF, TGF-β, MMPs, HIF-1α, IL-6, IL-33, Bcl-x, vimentin, and snail.
Conclusions:
- The developed nano-based therapeutic strategy shows significant potential for efficient cancer therapy.
- Combined targeting of the p68/STAT3 axis offers a promising approach for cancer treatment.
- Further investigation of this nano-therapeutic strategy is warranted for clinical applications.
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