Effects of Paclitaxel on human lung cancer cell lines in vitro and in vivo

摘要

AIMS:Paclitaxel (PTX) is an inhibitor of microtubule function and is also known to have an antiangiogenic activity.In the present paper we investigated the effect of PTX on human lung cancer cell lines in vivo and in vitro to elucidate the correlation between the resistance to PTX under normoxic conditions.METHODS AND RESULTS:First,we established human lung adenocarcinoma cancer cell lines,PC14PE6 and H441 cells,which stably possess one of following reporter plasmids; pEF/Luc which constitutively expresses luciferase gene and p5HRE/ CMVmp-Luc which expresses luciferase gene only under hypoxic conditions (PC14PE6 /EF-Luc,PC14PE6/ 5HRE-Luc,H441/EF-Luc and H441/5HRE-Luc) for orthotopic lung cancer models and monitor the progression of lung cancer by in vivo bioluminescence imaging system,which enables us to monitor the growth and the hypoxic area of tumors growing in the body of mice non-invasively repeatedly.We have evaluated its effect with orthotopic lung cancer mouse model by using PC14PE6 and H441.We examined the effect of PTX with the tumor xenogeraft model and found that PC14PE6 cells were resistant to PTX and H441 cells were sensitive to PTX treatment.PTX significantly prolonged the survival of H441 lung cancer model,while it hardly influenced the survival of PC14EP6 lung cancer model.And then we also found that PTX didn’t induce cell death to PC14PE6 cells in vitro under both hypoxic and normoxic conditions even at 100 nM PTX concentration (Fig.4A).Contrast to PC14PE6,H441 cells showed significant sensitivity to PTX under normoxic conditions.In western blot analysis,the expression level of HIF-1αprotein was higher in PC14PE6 than in the H441.CONCLUSION:High level of HIF-1α protein expression may have some relation with PTX resistant in PC14PE6 cell line.