吡柔比星诱导膀胱癌细胞凋亡的实验研究及预防膀胱癌术后复发的效果

Apoptotic mechanisms of pirarubicin against bladder cancer and its clinical use for preventing postoperative tumor recurrence

目的 探讨吡柔比星诱导膀胱癌细胞凋亡的机制和膀胱内灌注预防术后复发的效果。 方法 采用MTT法、流式细胞术和透射电子显微镜技术 ,研究不同浓度的吡柔比星对人膀胱癌细胞株T2 4的抑制作用。对 6 0例经尿道电切术的膀胱移行细胞癌患者 ,术后以 30～ 40mg吡柔比星膀胱内灌注 ,观察预防复发的效果。 结果 吡柔比星浓度为 10mg/L和 10 0mg/L时 ,对T2 4细胞生长的抑制率分别为 80 %和 94% ,G1期前出现明显的凋亡峰 ,可见胞浆内空泡形成、核染色质凝聚等典型细胞凋亡特征。当浓度为 10 0 0mg/L时 ,细胞出现坏死特征。共 5 8例完成 1个以上疗程 ,平均随访 18.8个月 ,复发 5例 (8.6 % )。 结论 抑制癌细胞生长和诱导细胞凋亡甚至死亡是吡柔比星抗肿瘤的机制之一。用吡柔比星进行膀胱内灌注预防膀胱癌术后复发安全。

Objective To study the antitumor mechanisms of pirarubicin (THP) and its effect on preventing postoperative recurrence of superficial bladder cancer. Methods MTT assay, flow cytometry and transmission electron microscope were used to assess the effects of different concentration of THP on T24 cell line. THP 40 mg in 50 ml distil water was used intravesically in 60 patients with transitional cell carcinoma after TURBT to prevent tumor recurrence. Results T24 cells were suppressed significantly by THP in concentrations of 10 mg/L and 100 mg/L,the suppressive rates being 80% and 94% respectively. Apoptosis peak was evident before G1 phase. The characteristics of cell apoptosis, such as bubble formation in cytoplasm and condensed chromosome, were typically manifested. Cells became necrotic when the concentration of THP was 1 000 mg/L. One course of THP intravesical administration was completed in 58 cases. All patients were followed up for a mean of 18.8 months (range 6～24 months), and tumor recurred only in 5 cases (8.6%). Conclusions Suppression of tumor cell growth and inducing apoptosis, even necrosis, might be the main antitumor mechanisms of THP. Clinically, intravesical administration of THP after TURBT was effective and safe for preventing tumor recurrence.