- 作者: Sue Lin-Chao ; Chuck C.K Chao
- 作者服務機構: a Institute of Molecular Biology, Academia Sinica, Taipei, and; b Tumor Biology Laboratory, Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要: The influence of cisplatin, an anticancer agent, on DNA synthesis and cell cycle progression of a cisplatin-resistant cell line was investigated. Cell cycle analysis using flow cytometry showed that cytotoxic concentrations of cispla- tin caused a transient inhibition of parental HeLa cells at S phase, followed by accumulation at G2 phase. In contrast, the resistant cells progressed through the cell cycle without being affected by the same treatment. However, cell cycle distributions were the same in the resistant and the parental cells at IC50, the drug concentration inhibiting cell growth by 50%. Studies using a [3H]thy- midine incorporation technique also demonstrated a transient inhibition of DNA synthesis in HeLa cells by cisplatin; such inhibition was greatly reduced in the resistant cells. These data argue for the hypothesis that the inhibition of DNA synthesis is important in determining cisplatin-induced cytotoxicity. In addition, the accumulation of cells at Go/Gl by serum starvation was not effec- tive in the resistant cells compared to the parental cells, suggesting that the control of cell cycle exiting is also altered in the resistant cells. Taken together, these results support the notion that alterations in cell cycle control, in particu- lar G2 arrest, are important in determining the sensitivity or resistance of mammalian cells to cisplatin and may have a role in clinical protocols.
- 中文關鍵字: --
- 英文關鍵字: Cell cycle; Cisplatin; Drug resistance