[Sequence-dependent effect of docetaxel with gefitinib on the proliferation and signal protein expression of human lung adenocarcinoma cell SPC-A1]

Wenying Zhang, Weimin Zhang, Lin Wang, Jingxian Zheng, Feng Xiao
Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer 2011, 14 (5): 385-90

BACKGROUND AND OBJECTIVE: It has been proven that chemotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could not increase response for advanced non-small cell lung cancer (NSCLC), but its cellular mechanism was not well known. The aim of this study is to assess the effects of sequential administration of docetaxel and gefitinib on the cell proliferation and signal pathway of lung adenocarcinoma cell SPC-A1 and its cellular mechanism.

METHODS: The mutation of EGFR and K-ras gene 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 blot.

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 in cells treated with docetaxel and gefitinib concomitantly or gefitinib followed by docetaxel. However, sequential administration of gefitinib following docetaxel could remarkably increase the inhibition of docetaxel on cell proliferation. Docetaxel increased, and gefitinib decreased, the phosphorylation of EGFR and ERK respectively. The suppression of pEGFR and pERK induced by gefitinib could not be activated by docetaxel, whether 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 the expression of IGF-1R.

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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"