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 ºC 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.