以及在使用铂类似物反式-[PtCl(3-Hmpy)]进行电化学疗法的评估中。
and in Evaluation of Electrochemotherapy with -platinum Analogue trans-[PtCl(3-Hmpy)].
作者信息
Kranjc Simona, Cemazar Maja, Sersa Gregor, Scancar Janez, Grabner Sabina
机构信息
Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia.
University of Primorska, Faculty of Health Sciences, Izola, Slovenia.
出版信息
Radiol Oncol. 2017 Sep 14;51(3):295-306. doi: 10.1515/raon-2017-0034. eCollection 2017 Sep.
BACKGROUND
Cisplatin is used in cancer therapy, but its side effects and acquired resistance to cisplatin have led to the synthesis and evaluation of new platinum compounds. Recently, the synthesized platinum compound -[PtCl(3-Hmpy)] (3-Hmpy = 3-hydroxymethylpyridine) (compound ) showed a considerable cytotoxic and antitumour effectiveness. To improve compound cytotoxicity and antitumour effectiveness , electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy).
MATERIALS AND METHODS
, survival of sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive) was determined using a clonogenic assay after treatment with compound or cisplatin electrochemotherapy. , the antitumour effectiveness of electrochemotherapy with compound or cisplatin was evaluated using a tumour growth delay assay. In addition, platinum in the serum, tumours and platinum bound to the DNA in the cells were performed using inductively coupled plasma mass spectrometry.
RESULTS
, cell survival after treatment with compound electrochemotherapy was significantly decreased in all tested sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive). However, this effect was less pronounced compared to cisplatin. Interestingly, the enhancement factor (5-fold) of compound cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells. , the growth delay of subcutaneous tumours after treatment with compound electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound or cisplatin electrochemotherapy were approximately 2-fold higher compared to the drug treatment only, and the same increase of platinum bound to DNA was observed.
CONCLUSIONS
The obtained results and suggest compound as a potential antitumour agent in electrochemotherapy.
背景
顺铂用于癌症治疗，但其副作用以及对顺铂产生的获得性耐药性促使人们合成并评估新型铂化合物。最近，合成的铂化合物-[PtCl(3-Hmpy)]（3-Hmpy = 3-羟甲基吡啶）（化合物 ）显示出相当大的细胞毒性和抗肿瘤效果。为提高化合物 的细胞毒性和抗肿瘤效果，采用电穿孔作为药物递送方法来增加膜通透性（电化学疗法）。
材料与方法
使用克隆形成试验测定在用化合物 或顺铂进行电化学疗法处理后，对顺铂具有不同内在敏感性的肉瘤细胞（TBLCl2敏感、TBLCl2Pt耐药和SA-1中度敏感）的存活率。使用肿瘤生长延迟试验评估用化合物 或顺铂进行电化学疗法的抗肿瘤效果。此外，采用电感耦合等离子体质谱法检测血清、肿瘤中的铂以及细胞中与DNA结合的铂。
结果
在用化合物 进行电化学疗法处理后，所有对顺铂具有不同内在敏感性的测试肉瘤细胞（TBLCl2敏感、TBLCl2Pt耐药和SA-1中度敏感）的细胞存活率均显著降低。然而，与顺铂相比，这种效果不太明显。有趣的是，化合物 在顺铂敏感的TBLCl2细胞和顺铂耐药的TBLCl2Pt细胞中的细胞毒性增强因子（5倍）相同。在用化合物进行电化学疗法处理后，皮下肿瘤的生长延迟低于顺铂。在用顺铂或化合物 进行电化学疗法后获得的最高抗肿瘤效果出现在TBLCl2肿瘤中，分别导致67%和11%的肿瘤治愈。与顺铂相比，化合物 引起的动物体重减轻明显更小。此外，在用化合物 或顺铂进行电化学疗法后，肿瘤中的铂含量比仅药物治疗时高出约2倍，并且观察到与DNA结合的铂有相同程度的增加。
结论
所获得的结果 和 表明化合物 是电化学疗法中一种潜在的抗肿瘤药物。
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