HHP-10 Multidrug Resistance in Lung Cancer Cells
Abstract
Individuals diagnosed with cancer and a comorbid mental illness have an increased mortality and shorter survival time, than those diagnosed with cancer alone. Although there are several contributing factors, such as a later overall stage of diagnoses and other contributing comorbidities, an avenue that is likely a neglected contributor to these poorer outcomes is multidrug resistance (MDR), defined as a resistance to multiple drugs with similar mechanisms of action. An increase in expression of P-glycoprotein (Pgp), a drug transporter encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene, has been linked to MDR due to its ATP-dependent efflux of cytotoxic drugs. Interestingly, many drugs utilized for the treatment of mental illnesses are substrates for Pgp, potentially explaining poorer outcomes of patients with both mental illness and cancer. Patients diagnosed with schizophrenia are often treated with antipsychotic medications for various times prior to being diagnosed and treated for cancer. An in vitro model was established to assess if persistent treatment of human cancer cells with antipsychotics can induce resistance to cytotoxicity of chemotherapy drugs. Preliminary analyses demonstrate increases in ABCB1 expression and chemoresistance in cells treated with a chemotherapeutic agent at 6 to 9 months of treatment. Cells treated with antipsychotic medications show low levels of ABCB1 expression after 9 months of treatment. These data were collected as part of an ongoing study and the cell lines will be reevaluated for ABCB1 expression and chemoresistance after 12 months of treatment.
This work was supported by SC-INBRE grant P20GM103499-20
Keywords
ABCB1, PgP, MDR
HHP-10 Multidrug Resistance in Lung Cancer Cells
University Readiness Center Greatroom
Individuals diagnosed with cancer and a comorbid mental illness have an increased mortality and shorter survival time, than those diagnosed with cancer alone. Although there are several contributing factors, such as a later overall stage of diagnoses and other contributing comorbidities, an avenue that is likely a neglected contributor to these poorer outcomes is multidrug resistance (MDR), defined as a resistance to multiple drugs with similar mechanisms of action. An increase in expression of P-glycoprotein (Pgp), a drug transporter encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene, has been linked to MDR due to its ATP-dependent efflux of cytotoxic drugs. Interestingly, many drugs utilized for the treatment of mental illnesses are substrates for Pgp, potentially explaining poorer outcomes of patients with both mental illness and cancer. Patients diagnosed with schizophrenia are often treated with antipsychotic medications for various times prior to being diagnosed and treated for cancer. An in vitro model was established to assess if persistent treatment of human cancer cells with antipsychotics can induce resistance to cytotoxicity of chemotherapy drugs. Preliminary analyses demonstrate increases in ABCB1 expression and chemoresistance in cells treated with a chemotherapeutic agent at 6 to 9 months of treatment. Cells treated with antipsychotic medications show low levels of ABCB1 expression after 9 months of treatment. These data were collected as part of an ongoing study and the cell lines will be reevaluated for ABCB1 expression and chemoresistance after 12 months of treatment.
This work was supported by SC-INBRE grant P20GM103499-20