Abstract
Anaplastic thyroid cancer (ATC) is an undifferentiated and advanced form of thyroid cancer, accompanied with a high ratio of epigenetic adjustment, which occurs more than genetic mutations. In this study, we aimed to evaluate the synergistic anticancer effect (in vitro and in vivo) of the new combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and sorafenib with radiation therapy in pre-clinical models of ATC. The ATC cell lines, YUMC-A1 and YUMC-A2, were isolated from the current patients who were treated with HNHA and sorafenib, either as monotherapy or combination therapy. Synergistic anticancer effect of the combination therapy on the intracellular signaling pathways and cell cycle was assessed via flow cytometry and immunoblot analysis. To examine tumor shrinkage activity in vivo, an ATC cell line-derived mouse xenograft model was used. Results showed that the combination therapy of HNHA and sorafenib with radiation promoted tumor suppression via caspase cleavage and cell cycle arrest in patient-derived ATC. In addition, the combination therapy of HNHA and sorafenib with radiation was more effective against ATC than therapy with HNHA or sorafenib with radiation. Thus, the combination of HNHA and sorafenib with radiation may be used as a novel curative approach for the treatment of ATC.
Highlights
The thyroid gland secretes thyroid hormones that play decisive roles in managing normal metabolism [1,2,3]
We indicated that the combination treatment of hydroxy-7-(2-naphthylthio) heptanomide (HNHA), sorafenib, and radiation had a lower IC50 in anaplastic thyroid cancer (ATC) than that of either drug alone with radiation
Synergistic anticancer activity of the HNHA, sorafenib, and radiation therapy was more effective than treatment with HNHA or sorafenib alone with radiation in patientderived ATC
Summary
The thyroid gland secretes thyroid hormones that play decisive roles in managing normal metabolism [1,2,3]. Recent studies have identified various molecules and mechanisms that are precisely associated with the poor clinical results in ATC [15,16]. Among these mechanisms, the synergistic anticancer effect of the histone deacetylase (HDAC) inhibitor or sorafenib and radiation-induced suppression of advanced cancer has been considered one of the probable reasons for poor clinical results [17,18,19]. The positive efficacy results obtained with HDAC inhibitors as anticancer agents resulted in the approval of HDAC inhibitors by the US Food and Drug Administration (USFDA) for the treatment of some cancer subtypes [20,21]. Sorafenib has been approved for the treatment of advanced renal cell carcinoma (RCC) and other human cancers [29,30,31,32]
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