Horiuchi A, Nikaido T, Mitsushita J, Toki T, Konishi I, Fujii S
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
Int J Cancer. 2000 Nov 15;88(4):640-4. doi: 10.1002/1097-0215(20001115)88:4<640::aid-ijc19>3.0.co;2-k.
Uterine leiomyosarcoma is an extremely malignant neoplasm with high rates of distant metastasis, and systemic chemotherapy is not particularly effective. Thus, the introduction of more active anticancer agents, or of a new drug delivery system, is urgently needed. Recently, electrochemotherapy has been introduced as a way of enhancing the cytotoxic effects of chemotherapeutic agents. This involves administering the drug in combination with electric pulses (which permeabilize tumor cell membranes and allow the drug to enter the cells). In particular, bleomycin (BLM) cannot cross the plasma membrane efficiently, but its cytotoxicity can be enhanced by electropermeabilization. The aim of the present study was to investigate the effect of low-voltage electroporation (EP) in combination with local BLM injection on the growth of uterine leiomyosarcoma in nude mice. Human uterine leiomyosarcoma cells (SK-LMS-1) were implanted subcutaneously into nude mice. Tumor growth in mice treated with EP (100 V/cm) plus BLM was compared with that in mice receiving BLM alone, EP alone, or no treatment (controls). Tissue BLM concentrations and histological analysis (including mitotic counts) were evaluated in tumor tissues. There was a significant reduction in tumor growth in mice that received EP with BLM. One hour after the treatment, the local BLM concentration was 10 times higher in the tumors that received EP with BLM than in those receiving only BLM. Moreover, the mitotic count was lower in the tumors that received EP plus BLM than in the controls. These results demonstrate the possible therapeutic value of low-voltage EP with BLM in human uterine leiomyosarcoma.
子宫平滑肌肉瘤是一种具有极高远处转移率的极恶性肿瘤，全身化疗效果并不特别显著。因此，迫切需要引入更有效的抗癌药物或新的给药系统。最近，电化学疗法作为一种增强化疗药物细胞毒性作用的方法被引入。这包括将药物与电脉冲联合使用（电脉冲可使肿瘤细胞膜通透性增加，使药物进入细胞）。特别是博来霉素（BLM）不能有效穿过质膜，但其细胞毒性可通过电穿孔增强。本研究的目的是探讨低电压电穿孔（EP）联合局部注射BLM对裸鼠子宫平滑肌肉瘤生长的影响。将人子宫平滑肌肉瘤细胞（SK-LMS-1）皮下植入裸鼠体内。将接受EP（100 V/cm）加BLM治疗的小鼠的肿瘤生长情况与单独接受BLM、单独接受EP或未接受治疗（对照组）的小鼠进行比较。评估肿瘤组织中的组织BLM浓度和组织学分析（包括有丝分裂计数）。接受EP加BLM治疗的小鼠肿瘤生长明显减少。治疗1小时后，接受EP加BLM治疗的肿瘤局部BLM浓度比仅接受BLM治疗的肿瘤高10倍。此外，接受EP加BLM治疗的肿瘤的有丝分裂计数低于对照组。这些结果证明了低电压EP联合BLM对人子宫平滑肌肉瘤可能具有治疗价值。
