AB061. Combination treatment of platinum based drugs in lung cancer, a possible way to overcome resistance?

Background: Lung cancer is the leading cause of death from cancer throughout the world. Its treatment with cytotoxic agents based on platinum has reached a plateau, which could not be improved in recent years in the response, the time to progression and the overall survival. The aim of this study was the evaluation of the combination of platinum based drugs treatment in lung cancer cell lines.

Methods: Combinations of Cisplatin with Carboplatin, Cisplatin with Nanoplatin and Cisplatin with Oxaliplatin treatment were tested on Small cell lung cancer (NCI-H1048) and non-small cell lung cancer (A549) cell lines. At indicated time-point, following 24 and 48 h incubation, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Statistical analysis was performed by GraphPad Prism. Gel electrophoresis of the DNA and RNA extracted from these lung cancer cell lines, was also performed for the evaluation of cisplatin and carboplatin effect on nucleic acid.

Results: In non-small cell lung cancer cells, following 24 and 48 h incubation, the combination of cisplatin (half dose) plus carboplatin (half dose) was found with higher cytotoxicity when compared to cisplatin (whole dose, 25 µM, P<0.001) alone, but not to carboplatin (whole dose, 150 µM) alone (equal cytotoxicity). In smaller doses combinations the combination proved with higher toxicity than both cisplatin (10 µM) and carboplatin alone (25 µM, P<0.001). In Small cell lung cancer the combination of cisplatin (half dose) plus carboplatin (half dose) was found with equal cytotoxicity to cisplatin (whole dose, 25 µM) alone and carboplatin (whole dose, 100 µM) alone following 24 and 48 h incubation. The other platinum combinations of cisplatin showed decreased apoptosis when compared to cisplatin alone (P<0.05). Results from electrophoresis showed that both cisplatin and carboplatin might affect DNA more when compared to RNA in both lung cancer cell lines.

Conclusions: In non-small cell lung cancer which is the predominant form of lung cancer, the combination of cisplatin and carboplatin might be a useful approach to overcome platinum resistance. Perhaps, cisplatin and carboplatin, both platinum based agents, result in better efficacy by affecting DNA in a different way which remains to be elucidated.

Keywords: Lung cancer; cisplatin; carboplatin; oxaliplatin