Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant
Open accessAbstract
BACKGROUND: Current therapeutic options for advanced pancreatic cancer have been largely disappointing with modest results at best, and though adjuvant therapy remains controversial, most remain in agreement that Gemcitabine should stand as part of any combination study. The inhibitor of apoptosis (IAP) protein Survivin is a key factor in maintaining apoptosis resistance, and its dominant-negative mutant (Survivin-T34A) has been shown to block Survivin, inducing caspase activation and apoptosis. METHODS: In this study, exosomes, collected from a melanoma cell line built to harbor a tetracycline-regulated Survivin-T34A, were plated on the pancreatic adenocarcinoma (MIA PaCa-2) cell line. Evaluation of the presence of Survivin-T34A in these exosomes followed by their ability to induce Gemcitabine-potentiative cell killing was the objective of this work. RESULTS: Here we show that exosomes collected in the absence of tetracycline (tet-off) from the engineered melanoma cell do contain Survivin-T34A and when used alone or in combination with Gemcitabine, induced a significant increase in apoptotic cell death when compared to Gemcitabine alone on a variety of pancreatic cancer cell lines. CONCLUSION: This exosomes/Survivin-T34A study shows that a new delivery method for anticancer proteins within the cancer microenvironment may prove useful in targeting cancers of the pancreas.
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In pancreatic cancer, exosomes loaded with T34A protein induced apoptosis and enhanced the gemcitabine-killing effect.
“In pancreatic cancer, it was shown that exosomes loaded with the survival protein-T34A protein induced apoptosis and enhanced the gemcitabine-killing effect [43].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [43]
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- Authors
- Aspe, J. R., Diaz Osterman, C. J., Jutzy, J. M. S., Deshields, S., Whang, S., & Wall, N. R.
- Affiliations
- Loma Linda University (US)
- Division of Biochemistry & Microbiology, Department of Basic Sciences Center for Health Disparities & Molecular Medicine, Loma Linda University Loma Linda CA USA
- Corresponding author
- Wall, Nathan R.
- Venue
- Journal of Extracellular Vesicles
- Publisher
- Wiley
- Published
- 2014-01
- Volume
- 3
- Issue
- 1
- ISSN
- 2001-3078 (ISSN-L)
- PMC
- PMC3929070
- OpenAlex
- W2043352210
- Cited by
- 126
- References
- 52
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 12 · 2023: 17 · 2022: 16 · 2021: 20 · 2020: 12 · 2019: 7 · 2018: 11 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Extracellular Vesicles (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Minority Health and Health Disparities (P20MD001632, P20MD001631)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- gemcitabine, pancreatic ductal adenocarcinoma, exosomes, inhibitor of apoptosis proteins, apoptosis resistance, exosome-mediated drug delivery, MIA PaCa-2 cells, combination therapy, tetracycline-regulated expression
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