Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms23073914
Keywords
mesothelioma; cancer stem cells (CSCs); molecular radiotherapy; radioimmunotherapy (RIT); liposomes; Lu-177
Funding
- National Cancer Institute [R01CA135358]
Ask authors/readers for more resources
The therapeutic effect of Lu-177-labeled immunoliposomes on CSCs of mesothelioma was evaluated in this study. The results showed that Lu-177-ILs inhibited proliferation, promoted apoptosis, and suppressed the expression of CD26 and CD24. Therefore, molecular radiotherapy targeting both CD26 and CD24 could be a promising approach for CSC-targeting therapy for MM.
Malignant mesothelioma (MM) is a lethal tumor originating in the mesothelium with high chemotherapeutic resistance. Cancer stem cells (CSCs) persist in tumors and are critical targets responsible for tumor resistance and recurrence. The identification and characterization of CSCs may help develop effective treatment for MM. The objective of this study was to evaluate the therapeutic effect of molecular targeted radiotherapy by Lu-177-labeled immunoliposomes (Lu-177-ILs) on CSCs of mesothelioma. MM CSCs were sorted based on CD26/CD24 expression level and their functional significances were established by small interference RNA. CSC potential of MM was evaluated for drug resistance, cell invasion, and cell growth rate in vitro. CSC metabolism was evaluated with the uptake of F-18-FDG. Therapeutic effects of Lu-177-labeled immunoliposomes targeting CD26 and CD24 were evaluated in vitro through proliferation and apoptotic assays. CSCs sorted from H28 cells exhibited significant drug resistance and enhanced proliferative activity as well as increased metabolism indicated by higher F-18-FDG uptake. Treatment with Lu-177-ILs, compared with Lu-177-CL and ILs, showed enhanced therapeutic effects on inhibition of proliferation, up-regulation of apoptosis, and suppression of CD26 and CD24 expression. Thus, our results suggest that molecular radiotherapy targeting both CD26 and CD24 could be a promising approach for CSC-targeting therapy for MM.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available