Effects Of Different Sequential Administration Of Gefitinib And Docetaxel On The NSCLC Cells

According to preclinical studies,there was synergism anti-tumor activity of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)and chemotherapy drugs.However, phase III randomized trials of multicenter showed that continuous daily administration of EGFR-TKIs in combination with conventional chemotherapy doublets as frontline therapy have failed to improve survival in patients with advanced non-small cell lung cancer(NSCLC).Close year,the clinical study of sequential therapy of EGFR-TKIs and chemotherapy for the treatment of NSCLC observed better effect than chemotherapy alone.But which is better of sequential therapis of EGFR-TKIs and chmotherapy is not understand. Different sequential administration of gefitinib which is EGFR-TKIs and docetaxel which is chemotherapy in this study, detect cell survival,cycle,apoptosis of PC-9,PC-9/G,A549 of NSCLC with different EGFR gene type, reseach whether to show up the difference or not from different sequential administration and posible mechanism of this difference.First, both gefitinib and docetaxel inhibited with different concentration gradient to three kinds of cells respectively,then the cytoactive was mesured by MTT assay, calculated 50%inhibit concentration(IC50) by graphic method; Experiment have 5 grup:control,gefitinib(G),docetaxel(D),gefitinib following docetaxel(G-D),docetaxel following gefitinib(D-G); the cytoactive was mesured by MTT assay,then cell survival was calculated with formula Detect cell survial rate of 5 grup by MTT assay;Cell cycle and apoptosis was marked with Annexin V/PE and staining with PI respectively, cell cycle distribution and apoptosis was detected by flow cytometry. Cell cycle was analysed by software of Multicycle 3.0.Get the result:1. Both gefitinib and docetaxel inhibited the cell proliferation of three kinds of cells in a dose-dependent;2. Both schedule effect on inhibition of cell growth hither than gefitinib or docetaxel alone(P<0.05) and the cell survival decreased remarkably when docetaxel following gefitinib contract with gefitinib following docetaxel(P<0.05);3. Sequential administration of docetaxel following gefitinib can induce G2/M phase arrest,sequential administration of gefitinib following docetaxel can induce G0/G1 phase arrest;4. Sequential administration of gefitinib following docetaxel can decrease apoptosis of docetaxel-induced in PC-9 and PC-9/G(P<0.05) and sequential administration of docetaxel following gefitinib enhance apoptosis contract with gefitinib following docetaxel(P<0.05); Sequential administration of gefitinib following docetaxel no difference apoptosis contract with docetaxel alone and sequential administration of docetaxel following gefitinib no difference apoptosis contract with gefitinib following docetaxel in A549 (P>0.05).Hint:1. Docetaxel following gefitinib is optimal combination schedule;2. The synergism effects on the inhibition of cell growth are observed when gefitinib is sequentially administrated following docetaxel, which may be associated with anti-proliferation and double blockade of cell cycle and increased rate of apoptosis in EGFR mutate cells; The synergism effects on the inhibition of cell growth are observed when gefitinib is sequentially administrated following docetaxel, which may be associated with anti-proliferation and double blockade of cell cycle.