The Effects And Mechanism On The Proliferation Of Human Adenocarcinoma Cell SPC-A1 Of Gefitinib Combined With Docetaxel In Different Administration.

Background and Objective Previous clinic trials showed that the effect of chemotherapy with epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of advanced non-small cell lung cancer (NSCLC) is sequence-dependent. Previous studies showed that the effect on cell cycle might relate to nogg additive effect of EGFR-TKI following chemotherapy or the concomitant use. EFGR-TKI following chemotherapy on the cell proliferation of NSCLC shows synergistic effects, but its cellular mechanism still remains unknown. The present study aimed to assess the effects of sequential administration of docetaxel and gefitinib on the cell proliferation of lung adenocarcinoma cell SPC-A1 and to probe its cellular mechanism by observing the expression and phosphorylation of EGFR, ERK, AKT and Insulin-like growth factor 1 receptor (IGF-1R). Methods The EGFR and K-ras gene mutation were examined by qPCR-HRM. MTT assay was used to measure the cell proliferation. The expression and phosphorylation of EGFR, ERK, AKT and IGF-1R were determined by western blotting. Results No EGFR or K-ras gene mutation was found in SPC-A1 cells. Compared with docetaxel or gefitinib alone, no synergistic effects on the cell proliferation were observed when cells were treated with docetaxel and gefitinib concomitantly or when gefitinib was used followed by docetaxel. However, sequential administration of gefitinib following docetaxel remarkably enhanced the inhibition of docetaxel on cell proliferation. Docetaxel increased, and gefitinib decreased, the phosphorylation of EGFR and ERK respectively. The phosphorylation of EGFR and ERK induced by docetaxel was significantly suppressed by subsequent exposure to gefitinib, but not by concomitant use of gefitinib. The gefitinib induced suppression of both pEGFR and pERK could not be activated by docetaxel, no matter used simultaneously or subsequently. No significant effects on the expression of AKT and p-AKT were found when docetaxel and gefitinib were administered simultaneously or sequentially. Docetaxel decreased, and gefitinib exerted no significant effect on, the expression of IGF-1R, respectively. Compared with docetaxel alone,no significant difference of IGF-1R expression was found when gefitinib was administered following docetaxel. Conclusion The phosphorylation of both EGFR and ERK, not the phosphorylation of AKT or the expression of IGFR, may contribute to the synergistic effects of EFGR-TKI following chemotherapy on the cell proliferation of NSCLC.