Cyclopentenylcytosine does not enhance cisplatin-induced radiosensitization in human lung tumour cells

Abstract

The search for agents that enhance the effect of ionizing radiation has been an object of study for decades. In this study, the sensitizing properties of cyclopentenylcytosine (CPEC) on radiation and cisplatin-induced radiosensitization in human squamous lung carcinoma cells were investigated. Human lung tumour SW-1573 cells (SWp, parental; SWg, gemcitabine-resistant) were incubated with CPEC and cisplatin and subsequently irradiated with different doses of γ-rays. Clonogenic survival was determined to measure the effectiveness of the treatments. CPEC (1 or 2 μM) treatment for 4 h decreased the plating efficiency to 75 and 50% in SWp and SWg cells, respectively. In the SWg cells, 0.1 and 1 μM CPEC for 4 h enhanced the cell killing effect of cisplatin. However, an increase was not noted in the SWp cells. Due to the moderate toxicity of 1 μM for 4 h, this CPEC dose was used in the radiosensitization experiments. However, CPEC neither radiosensitized the lung tumour cells nor enhanced the radiosensitizing effect of cisplatin. A 2-h incubation with 4 μM cisplatin also decreased the plating efficiency to 75-80% in the two cell lines. Using this cisplatin dose, radiosensitization was obtained in the two cell lines. Although cisplatin treatment clearly radiosensitized the lung tumour cells, CPEC treatment did not. Cisplatin-induced radiosensitization was also not enhanced by CPEC.

Figure 1

The toxicity of CPEC alone in SWp cells. Surviving fraction is plotted as a function of incubation time with 1 and 2 μM of CPEC. Means with standard errors of at least three separate experiments are shown.

Figure 2

Sensitization of cisplatin (2 h) by pre-incubation for 2 h with 0, 0.1 or 1 μM CPEC in (A) SWp and (B) SWg cells. Means with standard errors of at least three experiments are shown.

Figure 3

Survival curves of (A) SWp and (B) SWg cells after radiation only (□); radiation + preincubation with 1 μM CPEC (▾); radiation + preincubation with 4 μM cisplatin (▴) and radiation + 1 μM CPEC + 4 μM cisplatin (○). Means with standard errors of at least three experiments are shown. Data of survival curves of combined treatments are corrected for the toxicity of CPEC only, cisplatin only and CPEC + cisplatin.