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. 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. 1. Introduction As we all know, cancer has become the leading killer that endangers human health, with the highest morbidity and mortality. Undoubtedly, radiotherapy, chemotherapy, thermotherapy, and biotherapy all contribute to antitumor treatment to a great extent, but each has its own advantages and disadvantages, and any of them can hardly thoroughly cure cancer. Inspiring, extensive treatment, a joint healing strategy predicated on multidiscipline and (or) multimethod by a particular way because of their particular properties, shows an excellent prospect of malignancy treatment. It isn’t a straightforward overlap of some protocols but is certainly put into make use of rationally to check each other’s advantages, leading to a highly effective synergism [1]. Research have shown the fact that combination of a lot more than two healing regimens will get better antitumor results than the monotherapies included [1C5]. Inside our prior study, we mixed suicide gene naturally, inner irradiation of nuclide, and magnetic liquid hyperthermia (MFH) to take care of hepatoma by using magnetic nanoparticles as hinges. Dinaciclib cell signaling At length, pHRE-Egr1-HSV-TK was transfected into hepatoma cells through the use of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles (PEI-MZF-NPs) as the gene transfer vector, and SIRT3 131I-antiAFP McAb-GCV-BSA-NPs were intervened into hepatoma subsequently, and the tumors were directionally heated within an alternating magnetic field by adopting PEI-MZF-NPs as magnetic mass media. Hence, while 131I and hyperthermia eliminating tumor cells, nuclide irradiation allowed the Egr1 promotor to induce HSV-TK gene expressing, as well as the appearance could possibly be specifically improved by HRE in hypoxic solid tumor, causing a multiple targeted killing effect of genes, Dinaciclib cell signaling radionuclide and hyperpyrexia against hepatoma. The results exhibited that this radionuclide-gene combined with MFH had a good therapeutic effect on hepatoma, far better than any of the monotherapies; furthermore, no significant side effects were found [1]. It might be an applicable strategy for hepatic cancer treatment. However, how did the combination therapy exert therapeutic effects on hepatoma? What was the mechanism? This was unclear. It is comprehended that radiotherapy, chemotherapy, gene therapy, and thermotherapy have their own antitumor mechanisms, which are comprehensive and complicated. They may play antitumor functions in various ways. For instance, they may induce tumor cell apoptosis, restrain cell proliferation, inhibit tumor angiogenesis, or induce necrocytosis. Their antitumor effects may also be the result of joint action of various ways [6C9]. In the current study, to further investigate the antihepatoma effect of the radionuclide-gene therapy combined with MFH, explore the possible mechanisms at tissue, cellular, and molecular levels, and provide theoretical evidences and experimental data for its clinical application, the apoptotic induction of the combination therapy was examined; the expression changes of the proteins related to apoptosis such as survivin, livin, bcl-2, p53, and nucleus protein Dinaciclib cell signaling Ki67 involved with cell proliferation had been analyzed; MVD and VEGF.