Heinzelmann Joana, Hecht Sabine, Vogt Alexander Ruben, Siebolts Udo, Kaatzsch Peter, Viestenz Arne
Department of Ophthalmology, University Hospital Halle-Wittenberg, 06120 Halle, Germany.
Institute of Pathology, University Hospital Halle-Wittenberg, 06112 Halle, Germany.
J Clin Med. 2023 Jan 30;12(3):1087. doi: 10.3390/jcm12031087.
Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetitive application.
Tumor spheroids of three CM cell lines (CRMM1, CRMM2, CM2005.1) were treated repetitively with ECT using the chemotherapeutic agent bleomycin on days 3, 5, and 7 of culture. Application of bleomycin alone and electroporation alone served as controls. The cytotoxic effect was analyzed on day 10 compared to untreated control using an independent t-test. The spheroid outgrowth rate was measured.
CM tumor spheroid size (median value: 78%, SD: 32%) and viability (median value: 11%, SD: 11%) were dramatically reduced after repetitive ECT treatment (-value < 0.001). Decreased proliferation capacity (down to 8%) and an increase of apoptotic cells were observed. In most repetitive ECT-treated spheroids, no viable or proliferating cells were detected. Only 33-40% of repetitive ECT-treated spheroids exhibited single outgrowing cells with a delay of time up to 38 days.
Repetitive ECT application effectively induces cytotoxic effects in CM spheroids by inducing apoptosis, inhibiting proliferation and decreasing the percentage of surviving tumor cells. Thus, repetitive ECT results in improved antitumor effectiveness in CM and could be an alternative therapy option.
结膜黑色素瘤（CM）与高局部复发率和低生存率相关。需要新的治疗选择来降低复发率。本研究的目的是证明重复应用电化学疗法（ECT）对CM的疗效改善。
在培养的第3、5和7天，使用化疗药物博来霉素对三种CM细胞系（CRMM1、CRMM2、CM2005.1）的肿瘤球体进行重复ECT治疗。单独应用博来霉素和单独进行电穿孔作为对照。与未处理的对照相比，在第10天使用独立t检验分析细胞毒性作用。测量球体生长率。
重复ECT治疗后，CM肿瘤球体大小（中位数：78%，标准差：32%）和活力（中位数：11%，标准差：11%）显著降低（P值<0.001）。观察到增殖能力下降（降至8%）和凋亡细胞增加。在大多数接受重复ECT治疗的球体中，未检测到存活或增殖的细胞。仅33%-40%接受重复ECT治疗的球体表现出单个生长的细胞，延迟时间长达38天。
重复应用ECT通过诱导凋亡、抑制增殖和降低存活肿瘤细胞百分比，有效诱导CM球体的细胞毒性作用。因此，重复ECT可提高对CM的抗肿瘤疗效，可能是一种替代治疗选择。
