Objective: The combination of two or more drugs with different mechanisms is a promising strategy for cancer treatment, and radioimmunotherapy (RIT) is a trending antitumor strategy. Radiotherapy (RT) can promote and activate antitumor immune effects, and immunotherapy can strengthen the effects of selective internal radiotherapy (SIRT); the RIT combination is synergistic and can overcome the adverse side effects of monotherapy. In this study, we developed a radioimmunoconjugate (RIC)-the iodine-131 (131I)-labeled caerin 1.1 peptide-to treat human anaplastic thyroid cancer (ATC).
Methods: Antitumor activity of caerin 1.1 peptide was determined by MTT assay, plate colony formation and cell wound scratch assays, and the mechanism of the inhibition of carein 1.1 peptide on the growth of CAL-62 cells was identified by cell cycle and western blot. Then, we investigated the efficacy of the caerin 1.1 peptide as a single drug and the 131I-labeled caerin 1.1 peptide for ATC. H&E and TUNEL staining was performed to detect dead cells in the tumor tissue sections.
Results: We found that caerin 1.1 arrested cells in the S phase to induce apoptosis and inhibited tumor growth to inhibit phosphorylation of Akt. In vivo, the iodine-131 (131I)-labeled caerin 1.1 peptide achieved better antitumor efficacy than radiotherapy alone and showed a good biosafety profile.
Conclusions: Our study demonstrates for the first time that the iodine-131 (131I)-labeled caerin 1.1 peptide can inhibit CAL-62 tumor growth and migration. The iodine-131 (131I)-labeled caerin 1.1 peptide, which represents a radioimmunotherapy strategy based on the combination of SIRT with a peptide-drug conjugate, could provide a treatment means for the radical cure of ATC.
Keywords: Anaplastic thyroid cancer; CAL-62 cell; Caerin 1.1 peptide; Iodine-131; Radioimmunotherapy.