Title:Insights into Nano-Photo-Thermal Therapy of Cancer: The Kinetics of Cell Death and Effect on Cell Cycle
Volume: 20
Issue: 5
Author(s): Mousa Tabei, Elham Zeinizade, Jaber Beik, S. Kamran Kamrava, Zahra Nasiri, Habib Ghaznavi*Ali Shakeri-Zadeh*
Affiliation:
- Department of Pharmaceutical Research Centre, Zahedan University of Medical Sciences (ZaUMS), Zahedan,Iran
- Medical Physics Department, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran,Iran
Keywords:
Nano-photo-thermal therapy, gold nanoparticles, folic acid, apoptosis, radiotherapy, MTT assay.
Abstract:
Background: Despite considerable advances in nano-photo-thermal therapy (NPTT), there have been
a few studies reporting in-depth kinetics of cell death triggered by such a new modality of cancer treatment.
Objective: In this study, we aimed to (1) investigate the cell death pathways regulating the apoptotic responses
to NPTT; and (2) ascertain the effect of NPTT on cell cycle progression.
Methods: Folate conjugated gold nanoparticle (F-AuNP) was firstly synthesized, characterized and then assessed
to determine its potentials in targeted NPTT. The experiments were conducted on KB nasopharyngeal
cancer cells overexpressing folate receptors (FRs), as the model, and L929 normal fibroblast cells with a low
level of FRs, as the control. Cytotoxicity was evaluated by MTT assay and the cell death mode (i.e., necrosis or
apoptosis) was determined through AnnexinV/FITC-propidium iodide staining. Next, the gene expression profiles
of some key apoptotic factors involved in the mitochondrial signaling pathway were investigated using
RT-qPCR. Finally, cell cycle phase distribution was investigated at different time points post NPTT using flow
cytometric analysis.
Results: The obtained results showed that KB cell death following targeted NPTT was greater than that observed
for L929 cells. The majority of KB cell death following NPTT was related to apoptosis. RT-qPCR analysis
indicated that the elevated expression of Bax along with the depressed expression of Bcl-xL, Survivin and
XIAP may involve in the regulation of apoptosis in response to NPTT. Flow cytometric analysis manifested that
16-24 hours after NPTT, the major proportion of KB cells was in the most radiosensitive phases of the cell cycle
(G2/M).
Conclusion: This study extended the understanding of the signaling pathway involved in the apoptotic response
to NPTT. Moreover, the potential effect of NPTT on sensitizing cancer cells to subsequent radiation therapy was
highlighted.