TCRP1 contributes to cisplatin resistance by preventing Pol ß degradation in lung cancer cells.

ABSTRACT

Cisplatin (DDP) is the first-line chemotherapy drug widely used for the treatment of lung cancer patients, whereas the majority of cancer patients will eventually show resistance to DDP. The mechanisms responsible for DDP resistance are not fully understood. Tongue cancer resistance-associated protein 1 (TCRP1) gene was recently cloned and reported to specially mediate DDP resistance in human oral squamous cell carcinoma (OSCC) cells. However, the mechanisms of TCRP1-mediated DDP resistance are far from clear, and whether TCRP1 participates in DDP resistance in lung cancer cells remains unknown. Here, we show that TCRP1 contributes to DDP resistance in lung cancer cells. Knockdown of TCRP1 sensitizes the cells to DDP and increases the DDP-induced DNA damage. We have identified that Pol ß is associated with DDP resistance, and Pol ß knockdown delays the repair of DDP-induced DNA damage in A549/DDP cells. We find TCRP1 interacts with Pol ß in lung cancer cells. Moreover, TCRP1 knockdown decreases the level of Pol ß and increases the level of its ubiquitination. These results suggest that TCRP1 contributes to DDP resistance through the prevention of Pol ß degradation in lung cancer cells. These findings provide new insights into chemoresistance and may contribute to prevention and reversal of DDP resistance in treatment of lung cancer in the future.