Abstract
ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined chemotherapy, which is often not fully effective for the appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches for this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel and investigated the characteristics of these cells by analyzing the profile of gene expression and comparing it with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment resulted in a reduction of viability and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro.
Highlights
Thyroid cancer (TC) is the most common endocrine carcinoma, accounting for 1–2%of cancer cases worldwide [1]
While papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), which account for more than 95% of tumors, are mostly responsive to the current treatment based on surgery and following radioiodine therapy, resulting in an overall survival rate of over 90% within 10 years, anaplastic thyroid cancer (ATC) are a very rare, but extremely aggressive form of thyroid malignancy
In the first set of experiments, we evaluated the response to PTX in both wild-type and resistant ATC cell lines
Summary
Thyroid cancer (TC) is the most common endocrine carcinoma, accounting for 1–2%of cancer cases worldwide [1]. While PTC and FTC, which account for more than 95% of tumors, are mostly responsive to the current treatment based on surgery and following radioiodine therapy, resulting in an overall survival rate of over 90% within 10 years, ATCs are a very rare, but extremely aggressive form of thyroid malignancy. They are mostly diagnosed as stage IV disease [1], often are not resectable, and do not respond to radioactive iodine ablation for their undifferentiated phenotype due to the loss of thyroid-specific gene expression [2]. For these reasons and considering its extremely fast-growing and aggressive nature, ATC, representing less than 2% of all thyroid malignancies, is responsible for 20–50% of thyroid cancer mortality [3].
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