Decitabine nanoparticles supplement docetaxel in the treatment of non-small cell lung cancer (NSCLC)

Docetaxel is one of the most effective chemotherapeutic agents in the treatment of non-small cell lung cancer. Unfortunately, there is altered response to DTX due to resistance. DNA methylation, an epigenetic event, plays a vital role in cancer and chemotherapy drug resistance. Exploiting the gene reactivation by using epigenetically acting agents in combination with cytotoxic therapies, is a strategy of huge clinical relevance. To study the effects of co-administration of epigenetic drug decitabine and docetaxel, we had used human epithelial lung cancer cell lines (A549). A549 cells were cultured and maintained in DMEM, supplemented with 10% (v/v) FBS and 1% (v/v) penicillin/streptomycin (100,000 U/l penicillin, 100 mg/l streptomycin), at 37 °C in a humidified atmosphere containing 5% carbon dioxide. The cell viability was studied by MTT assay. Decitabine, docetaxwl, decitabine + docetaxel, decitabine nanoparticles + docetaxel were dissolved in the culture medium and added to 96 well plates in different dilutions. The IC50 of DTX and DEC on A549 cells were found to be 0.1 μM and 11.7 μM, respectively. Thereafter, dose dependent response was noted by decreasing the dose of DEC to find a combination dose. The combination of decitabine nanoparticles + docetaxel was found to be more cytotoxic and appears to influence the natural history of NSCLC in a significant manner.