Abstract:

Objective   To construct a paclitaxel (PTX)-resistant human cervical carcinoma cell line and observe the effects of N-acetylcysteine (NAC) on resistance to PTX in the cells.  Methods   Hela cells were treated with PTX to construct the PTX-resistant Hela/PTX cell line. The cell shape, cell growth curves and drug resistance index as well as the cellular redox state and the taxol resistance gene 1 (Txr1) expression were observed or determined. Hela/PTX cells were treated with NAC, and the effects of NAC on resistance to PTX in the cells were observed.  Results   After Hela cells were treated with PTX for 10 months, the PTX-resistant cervical carcinoma Hela/PTX cells could be obtained, which grew well in 500μg/L of PTX. Compared with Hela cells, the size of Hela/PTX cells was larger, and there were more cytoplasmic granules in them. The population doubling time for Hela/PTX cells was 1.32 times of that for Hela cells. Hela/PTX cells manifested a stronger resistance to PTX than Hela cells did with the resistance index of 122.69. They had higher levels of reactive oxygen species (ROS) and Txr1 mRNA, a lower level of reduced glutathione(GSH), and lower activities of superoxide dismutase, catalase and glutathione peroxidase than Hela cells. There was no significant difference between Hela/PTX and Hela cells in the level of oxidized glutathione (GSSG) or the GSH to GSSG ratio. After Hela/PTX cells were treated with NAC, the levels of ROS and Txr1 mRNA in them decreased, and they were more sensitive to PTX.  Conclusion   In Hela/PTX cells, which resisted to PTX, there was a redox imbalance, and the Txr1 transcripts increased. NAC could reduce the levels of ROS and Txrl mRNA in Hela/PTX cells and reversed the sensitivity of them to PTX.

Key words: Cervical neoplasms; Paclitaxel; Drug resistance; N-acetylcysteine; Reactive oxygen species; Taxol resistance gene 1