AI Article Synopsis
- Cisplatin (DDP) is a common chemotherapy drug used for treating cervical cancer, particularly in advanced cases or for patients wishing to preserve fertility; TRAIL is a protein that can selectively induce death in cancer cells.
- Human chorion-derived mesenchymal stem cells (hCD-MSCs) were modified to enhance TRAIL production and their exosomes (hCD-MSCs-Exo) were developed as delivery vehicles for DDP via a method called electroporation.
- The combination of DDP and hCD-MSCs-Exo demonstrated improved effectiveness in reducing cancer cell proliferation and promoting apoptosis in vitro and in vivo, with minimal toxicity, indicating a promising therapeutic approach for cervical cancer treatment.
Article Abstract
Background: Cisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources.
Methods: Human chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCs) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-Exo) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-Exo) were fabricated by loading DDP into hCD-MSCs-Exo via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-Exo in vivo.
Results: Compared with hCD-MSCs-Exo, hCD-MSCs-Exo weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-Exo were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-Exo alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-Exo evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-Exo showed favorable biosafety in vivo.
Conclusions: DDP & hCD-MSCs-Exo nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536590 | PMC |
| http://dx.doi.org/10.1186/s13287-024-04006-6 | DOI Listing |
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