Effects of Dihydrotanshinone I on proliferation and invasiveness of Paclitaxel-resistant anaplastic thyroid cancer cells

ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In the 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 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 of this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel, to investigate the characteristics of these cells by analyzing the profile of gene expression and comparing 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 results in a reduction of cell 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. mRNA profiles of SW1736 and 8505C paclitaxel-resistant cells.