Long-term chronic exposure to benzo[a]pyrene and catechol induced multidrug resistance in lung cancer cells

Multiple studies have raised concerns about the impact of long-term exposure to environmental pollutants on the occurrence and progression of cancer, but little is known about how these compounds affect the treatment of cancer patients. In this work, two common pollutants including benzo [a]pyrene (B [a]P) and catechol (CL) were tested for their chronic effects on the efficacy of common chemotherapeutic drug in lung cancer (A549) cells. Both pollutants were unlikely to be the substrates of ABC transporters, as their toxicity was unaffected by ABC transporter inhibitors. However, their repeated exposure led to the generation of chemoresistance to doxorubicin (DOX) and cisplatin (CDDP), indicating the formation of multidrug-resistance (MDR) cells. Compared with DOX-resistant cells, decreased expression of ABC transporters but increased responses were found in pollutants-resistant cells. In addition, pollutants-resistant cells were more potent in up-regulating anti-apoptosis, proliferation, and migration pathways, which were confirmed by the wound-healing and apoptosis assays. Overall, these results indicated a distinct MDR mechanism induced by non-substrate pollutants, and could be beneficial for understanding the environmental risk of pollutants in their "safe" concentrations.