CXCR4, A Potential Predictive Marker for Docetaxel Sensitivity in Gastric Cancer

LI XIE; JIA WEI; XIAOPING QIAN; GANG CHEN; LIXIA YU; YITAO DING; BAORUI LIU

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Figure 1.
Drug resistance phenotype of BGC-823/DOC. A: Morphology comparison between parental BGC-823 cells and docetaxel resistant BGC-823/DOC cells (100×). B: Cytotoxic effect of docetaxel on BGC-823 and BGC-823/DOC cells. C: Cell cycle arrest and apoptosis induced by docetaxel (0.5 μM) in BGC-823 and BGC-823/DOC cells. P, Parental cells; R, resistant cells; con, control without docetaxel treatment; 48, cells harvested after exposure to docetaxel for 48 h; 72, cells harvested after exposure to docetaxel for 72 h.
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Figure 2.
Gene ontology analysis of genes changed by treatment of BGC-823/DOC cells with docetaxel. The expression of 328 and 155 genes which increased (up-regulated) and decreased (down-regulated) significantly, respectively, was analysed by gene ontology.
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Figure 3.
CXCR4 mRNA is related to docetaxel sensitivity in gastric cancer. A: Correlation between CXCR4 mRNA expression levels and inhibition rate of docetaxel. B: Mean CXCR4 expression levels of the sensitive and resistant groups (mean CXCR4 expression ± standard deviation).
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Figure 4.
The possible role of CXCR4 in docetaxel sensitivity. A: CXCR4 mRNA expression levels were up-regulated when BGC-823 cells were treated with docetaxel at the IC₅₀ (10 nM) for 2 to 12 h; B: CXCR4 mRNA expression levels decreased during the induction of resistance for BGC-823 cells; C: AMD3100 (200 ng/ml) enhanced cytotoxicity of docetaxel on MKN-45 cells using an MTT assay (mean inhibition rates ± standard deviation).
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Figure 5.
CXCR4 signaling pathway and possible role in docetaxel (DOC) sensitivity. The signal pathway is plotted according to Wong et al. (28). Blocking the signaling pathway with antagonists or siRNA against PKA (29), AKT (30), NF-κB (31) and ERK(32) can sensitise cancer cells to Doc. The tvarious isoforms of PKC can also affect the Doc sensitivity. Medicines which can down-regulate NF-κB and ERK or phosphorylate BAD (35) can also change chemosensitivity to Doc. Thus, the signal pathway activated by CXCR4 was related closely to the sensitivity to Doc.