TCRP1 expression is associated with platinum sensitivity in human lung and ovarian cancer cells

摘要

Platinum-based drugs, including cisplatin (DDP) and oxaliplatin (L-OHP), are among the most potent chemotherapy drugs, and are widely utilized for the treatment of human lung and ovarian cancer. However, certain patients do not respond to platinum-based agents, and even those who initially benefit from the treatment will eventually exhibit resistance to these drugs. Although certain factors have been investigated for their potential to predict platinum resistance, more effective predictors for the improved management of patients with lung and ovarian cancer are required. Tongue cancer resistance-associated protein 1 (TCRP1) is a newly identified gene, which was cloned from a multi-drug resistant cell line of tongue cancer. Previous data has shown that TCRP1 is able to mediate DDP resistance in human oral squamous cell carcinoma cells. However, the contribution of TCRP1 to the resistance of platinum agents in human lung and ovarian cancer cells remains to be elucidated. Our previous study showed that TCRP1 expression levels in samples of lung and ovarian cancer were significantly increased compared with normal controls. In the present study, it was demonstrated that TCRP1 contributed to the resistance to DDP and L-OHP in human lung and ovarian cancer cells. Knockdown of TCRP1 resensitized the cells to the platinum-based agents. The present study identified a positive correlation between TCRP1 expression and primary resistance to DDP and L-OHP in lung cancer cells. In addition, it was observed that cells treated with nuclear factor (NF)-κB inhibitor BAY 11–7082 displayed increased sensitivity to DDP and L-OHP. The results of the present study suggested that TCRP1 may be associated with resistance to DDP and L-OHP in lung and ovarian cancer cells, and the Akt/NF-κB signaling pathway may be involved in the functioning of TCRP1. These findings identify TCRP1 as a potential predictor of platinum resistance in the treatment of lung and ovarian cancer.