Effects of Paclitaxel and Docetaxel on EGFR-Expressing Human Carcinoma Cells Under Normoxic Versus Hypoxic Conditions In Vitro

Abstract

Human malignant tumors, such as non-small lung, breast, ovarian, head and neck, prostate, stomach and colorectal cancers express a number of growth factor receptors (e.g. EGFR or EGFR family members) that are regulated by tumor hypoxia and contribute to tumor growth and failure of cytotoxic therapy. Paclitaxel and docetaxel are indispensable substances in the treatment of these tumors. Despite the active clinical use of taxanes, little is known about their cytotoxic activity under hypoxia. The aim of the present work was to compare the cytotoxic effect of taxanes, paclitaxel and docetaxel on the EGFR-expressing carcinoma cell lines A431, MDA-MB-231 and NCI-H358 under normoxic and hypoxic conditions. The two taxanes caused different cell cycle distribution and varying aneuploid cell formation under hypoxia. EGFR-overexpressing carcinoma cells showed hypoxia to severely affect the cytotoxicity of paclitaxel, whereas docetaxel preserved its tumor cellkilling activity even at lowest concentrations (0.5 nM), as was observed for both taxanes under normoxia.

Keywords:

• Cancer
• hypoxia
• paclitaxel
• docetaxel
• epidermal growth factor receptor
• epidermal growth factor receptor (EGFR)