Investigation of cytotoxic and anti-metastatic effects of carboplati̇n on etoposide-resistant A549 cell line

Lung cancer constitute the largest percentage of deaths from cancer in men and women. In addition to its high incidence, non-small cell lung cancer (NSCLC) is one of the deadly diseases that significantly affects quality of life and longevity of patients. In these disease, firstly acquired resistance to drugs administered as chemotherapeutic agents also show highly negative results in patients. Adjuvant therapies for treatment of acquired resistance is very important in increasing quality of life and longevity of patients. Etoposide is one of most used chemotherapeutics in clinics for NSCLC patients. In spite of positive results for treatments, cancer cells can develop resistance against etoposide over time. Carboplatin is a platin-derived drug also used for non-small cell lung cancer (NSCLC) treatment. Its use in adjuvant therapy often demonstrates success. In this study, we first developed etoposide resistance on A549 non-small cell lung carcinoma cell line. We examined the cytotoxic effects of various doses of carboplatin on parental A549 cell line and etoposide-resistant A549/90E cell line. At IC50 values for carboplatin We determined changes in caspase-3 and MMP-2 enzyme activities in both cell lines at the determined doses of carboplatin. As a result, carboplatin were shown dose and time-dependent high cytotoxic effect on parental and resistant A549 cell lines. Carboplatin showed a 2.3-fold increase in caspase-3 enzyme activity on the A549/P cell line at a concentration of 15 μg/ml for 72 hours and a 13-fold increase in caspase-3 enzyme activity at the 12 μg/ml concentration on the A549/90E cell line. It showed a 1.95 fold decrease in MMP-2 enzyme activity on A549/P cell line at a concentration of 15 μg/ml for 72 hours and a 2.38-fold decrease in MMP-2 enzyme activity at the 12 μg/ml concentration on the A549/90E cell line.