Abstract: OBJECTIVE: To observe the effects of paclitaxel on human lung cancer cell lines with different p53 genotype in vitro. METHODS：A549 (wild-type p53)，H322 (mutant-type p53) and H1299 (absence-type p53) were exposed to paclitaxel at different concentrations (0.1，1.0，10，100，1 000 nmol/L) or different treatment times (4，12，24，48，96 h)，then MTT assay，flow cytometry and western blotting were used to analyze the effects of paclitaxel on cell growth rate，cell cycle progression，apoptosis and the expressions of acetyl-tubulin and p53 protein. At the same time，negative control group (no paclitaxel) and blank control group (only culture medium) were set up. RESULTS：The growth-inhibition effects of paclitaxel on the three human lung cancer cell lines increased along with the response time extension (P＜0.05). Paclitaxel of different concentrations also had different effects on each lung cancer cell line (P＜0.05). The IC50 (50% inhibitory concentration) of paclitaxel for A549 was lowest in the three cell lines，but the difference of chemosensitivity of those cells to paclitaxel was not significant (P＞0.05). For the time-dependent experiment，the induction of apoptosis was time-dependent (P＜0.05) and the percentage of G2/M phase was highest at 12 h when paclitaxel was 10 nmol/L. When treated with 1 000 nmol/L paclitaxel，A549 showed the time-dependent G2/M arrest (P＜0.05)，while H322 and H1299 had the greatest G2/M arrest at 24 h. Prolonging paclitaxel treatments (48 h or more) resulted in appearance of polyploidy cells in H1299. The two concentrations could induce time-dependent apoptosis，but the higher one caused apoptosis later than the lower one. During concentration-dependent experiments， the proportion of apoptosis was highest at 10 nmol/L paclitaxel，while the percentage of G2/M phase increased in parallel with the paclitaxel concentration，when the latter changed from 0.1 nmol/L to 100 nmol/L (P＜0.05). Apoptosis had no relationship with G2/M arrest (P＞0.05). Paclitacxel up-regulated acetyl-tubulin and wild-type p53 protein expressions in time-and concentration-dependent manner，with no influence on mutant-p53 protein. CONCLUSION：Paclitaxel could inhibit the growth of the three human lung cancer cell lines with different p53 status in vitro in time-dependent manner. Different paclitaxel concentrations also had different effects on each lung cancer cell line. Paclitaxel could up-regulate wild-p53 protein expression and induce both p53-dependent and p53-independent apoptosis pathways. p53 genotype of the cells altered the effect of high concentration paclitaxel on cycle arrest，but did not influence paclitaxel chemosensitivity.

Key words: lung neoplasms, paclitaxel, p53, apoptosis, cell cycle