Abstract
Our previous findings showed a good therapeutic effect of the combination of suicide gene HSV-TK, nuclide 131I, and magnetic fluid hyperthermia (MFH) on hepatoma by using magnetic nanoparticles as linkers, far better than any monotherapy involved, with no adverse effects. This combination therapy might be an eligible strategy to treat hepatic cancer. However, it is not clear how the combination regimen took the therapeutic effects. In the current study, to explore the possible mechanisms of radionuclide-gene therapy combined with MFH to treat hepatoma at tissue, cellular, and molecular levels and to provide theoretical and experimental data for its clinical application, we examined the apoptosis induction of the combination therapy and investigated the expression of the proteins related to apoptosis such as survivin, livin, bcl-2, p53, and nucleus protein Ki67 involved in cell proliferation, detected VEGF, and MVD involved in angiogenesis of tumor tissues and analyzed the pathologic changes after treatment. The results showed that the combination therapy significantly induced the hepatoma cell apoptosis. The expression of survivin, VEGF, bcl-2, p53, livin, Ki67, and VEGF proteins and microvascular density (MVD) were all decreased after treatment. The therapeutic mechanisms may be involved in the downregulation of Ki67 expression leading to tumor cell proliferation repression and inhibition of survivin, bcl-2, p53, and livin protein expression inducing tumor cell apoptosis, negatively regulating VEGF protein expression, and reducing vascular endothelial cells, which results in tumor angiogenesis inhibition and microvascular density decrease and tumor cell necrosis. These findings offer another basic data support and theoretical foundation for the clinical application of the combination therapy.
Highlights
As we all know, cancer has become the leading killer that endangers human health, with the highest morbidity and mortality
PHRE-Egr1HSV-TK was transfected into hepatoma cells by using PEIMn0.5Zn0.5Fe2O4 nanoparticles (PEI-MZF-NPs) as the gene transfer vector, and subsequently 131I-antiAFP McAbGCV-BSA-NPs were intervened into hepatoma, and the tumors were directionally heated in an alternating magnetic field by adopting PEI-MZF-NPs as magnetic media
The results of flow cytometry analysis showed that magnetic fluid hyperthermia (MFH), internal irradiation of nuclide 131I, and suicide gene TK driven by HRE/Egr1 all induced hepatoma cell apoptosis, but the joint application of these three took a much stronger effect
Summary
Cancer has become the leading killer that endangers human health, with the highest morbidity and mortality. Comprehensive treatment, a joint therapeutic strategy based on multidiscipline and (or) multimethod by a specific way in view of their respective properties, has shown a great potential for malignancy treatment It is not a simple overlap of some protocols but is put into use rationally to complement each other’s advantages, resulting in an effective. The results demonstrated that the radionuclide-gene combined with MFH had a good therapeutic effect on hepatoma, far better than any of the monotherapies; no significant side effects were found [1]. It might be an applicable strategy for hepatic cancer treatment. How did the combination therapy exert therapeutic effects on hepatoma? What was the mechanism? This was unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
