Preliminary Study On Antitumor And Radiosensitizing Effect Of Phenothiazines

ObjectivePhenothiazines was administered in vitro to observe its antitumor activity and radiosensitizing effect in human cervical carcinoma cell line HeLa and human glioma cell line U-251, and to investigate its antitumor activity and radiosensitizing effect in vivo. The experiment was also tried to clarify its mechanisms of action.MethodsMTT colorimetric assay was applied to detect cytotoxicity of phenothiazines. Cloning efficiency determined the radiosensitizing effect of the phenothiazines. The alteration of cell cycle was estimated using flow cytometry. Nude mice with human cervical carcinoma were established to observe the antitumor activity of trifluoperazine in vivo. And, its radiosensitizing effect in vivo was observed by transplanting ascites neoplasia S180 in Kunming mice' s brain. Apoptosis induction was detected using pathological samples.Results1. Consequences in vitroGrowth restrain was observed in HeLa and U-251 cell when administered with different dose of trifluoperazine (TFP) and phenothiazine, but theeffect of phenothiazine was awfully feeble, and it was much more stronger when the dose of TFP was 1X 10-5, 2X 10-5mol/L. The LD50 of the two cell lines is 9. 70X10-6mol/L (Hela) and 5.98X10-6mol/L (U-251) . The influence was increased concomitant with the increasing of compound concentration and culture time. Here we demonstrated that TFP increased the dose-dependent and time-dependent radiosensitivity in HeLa and U-251 cell, and it was less affected with phenothiazine. Cell cycle block was found in HeLa and U-251 cell cultured with TFP and received r-rays irradiation, and the effect was the highest peak in about 6 hours. 2. Therapeutic efficacy in vivoTFP showed dose-dependent inhibitory activity against nude mice bearing human cervical carcinoma cell line HeLa. It was expressed that TFP prolonged the mice life with brain tumor transplanted and reinforced the radiosensitivity of these mice. TFP induced apoptosis in the tumor cells, but not of normal cells around. Moreover, it enlarged the apoptosis induction of irradiation in the tumor cells.ConclusionsTFP had an ability of suppressing HeLa and U-251 cell in vitro, and it also enhanced the radiosensitivity of the two cell lines. The activity of TFP increased concomitant with the increasing of compound concentration. TFP blocked cell cycle in G0-G1 TFP expressed inhibitory activity against nude mice bearing human cervical carcinoma cell line HeLa, and it also showed antitumor activity and radiotherapy augmentation in tumor transplanted mice. TFP induced apoptosis in the tumor cells.