TTP mediates cisplatin-induced apoptosis of head and neck cancer cells by down-regulating the expression of Bcl-2

Abstract

The chemotherapeutic agent cisplatin is widely used for treatment of head and neck squamous cell carcinoma (HNSCC). B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein that is overexpressed in cancer cells and confers resistance to cisplatin. Thus, inhibition of Bcl-2 expression may enhance the cisplatin sensitivity of cancer cells. In this study, we report that the AU-rich element (ARE) binding protein tristetraprolin (TTP) inhibits the expression of Bcl-2 and enhances cisplatin sensitivity of HNSCC cells. Cisplatin-sensitive HNSCC cells express high levels of TTP and low levels of Bcl-2, while cisplatin-resistant HNSCC cells have low levels of TTP and high levels of Bcl-2. Inhibition of TTP expression using siRNA increases levels of Bcl-2 and decreases cisplatin sensitivity in HNSCC cells. On the contrary, overexpression of TTP decreases Bcl-2 expression and increases sensitivity to cisplatin. Together, the results of the present study suggest that TTP expression enhances cisplatin sensitivity in HNSCC cells by reducing levels of Bcl-2.