Although
epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are used as first-line agents for treating nonsquamous cell
lung cancer with EGFR mutation, there are many patients who have to receive these drugs following
platinum-based
chemotherapy. This study was designed to define whether exposure to
cisplatin could affect the sensitivity to EGFR TKIs because conflicting results have been presented. We established sublines that are resistant to
cisplatin from EGFR wild-type cells (A549 and H460) and EGFR mutant cells (PC-9 and HCC827). The EGFR-related signals were examined by Western blotting. MTT assay and the
trypan blue exclusion method were used for the in vitro study, while
tumor size and the SUV of the 18FDG-PET scans were measured in animal models. The IC50 value and apoptotic fractions after exposure to EGFR TKIs, such as
gefitinib,
erlotinib, and
BIBW 2992, were almost the same in the
cisplatin-resistant sublines compared to that of the parent cells. Although the baseline PTEN expression was reduced in the resistant cells, as was indicated in a previous study, the EGFR-related signals similarly responded to the EGFR TKIs. Furthermore, the reduced
tumor size and SUV of the 18FDG-PET of the implanted
tumor in nude mice according to
erlotinib treatment were not different between the resistant sublines and the parent cells. In conclusion, the acquired resistance to
cisplatin did not affect the sensitivity to EGFR TKIs in the EGFR mutant
lung cancer cells, and this should abrogate any concerns about the use of EGFR TKIs following
platinum-based
chemotherapy.