A Molecular Carrier to Transport and Deliver Cisplatin into Endometrial Cancer Cells
A Molecular Carrier to Transport and Deliver Cisplatin into Endometrial Cancer Cells
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DOI：
10.1111/j.1747-0285.2012.01337.x
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发表时间：
2012-07-01
影响因子：
3
通讯作者：
Mancini, Aldo
中科院分区：
文献类型：
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作者：
Borrelli, Antonella;Schiattarella, Antonietta;Mancini, Aldo
重组锰超氧化物歧化酶（rMnSOD-Lp）的前导肽充当分子载体。在存在rMnSOD-Lp、单独的顺铂（CC）或与rMnSOD-Lp缀合的顺铂（rMnSOD-Lp-CC）的情况下，对正常（MRC-5）和子宫内膜腺癌细胞（HTB-112）进行克隆形成试验。通过原子分光光度法吸光度测量递送到细胞中的铂。最后通过光镜和透射电镜观察肿瘤细胞和正常细胞的治疗效果。肿瘤细胞死亡的情况下，0.5 μ m顺铂本身是最小的，而在0.5 μ m的rMnSOD-Lp-CC的存在下，没有肿瘤细胞存活。原子吸收分析表明，rMnSOD-Lp-CC向HTB-112细胞中递送的顺铂比单独使用顺铂递送的量多约4倍。通过光镜观察，rMnSOD-Lp-CC处理的细胞显示出核和胞质碎裂的迹象，即由处理诱导的凋亡。rMnSOD-Lp-CC对子宫内膜癌细胞有显著的治疗作用，而对正常细胞的毒性很小。我们认为，rMnSOD-Lp值得考虑作为一种分子载体，将顺铂直接输送到肿瘤细胞，从而将其抗复制活性转化为特异性和选择性的抗肿瘤剂。
The leader peptide of a recombinant manganese superoxide dismutase (rMnSOD-Lp) acts as a molecular carrier. Clonogenic tests on normal (MRC-5) and endometrial adenocarcinoma cells (HTB-112) were carried out in the presence of rMnSOD-Lp, cisplatin alone (CC) or cisplatin conjugated to the rMnSOD-Lp (rMnSOD-Lp-CC). The platinum delivered into the cells was measured by atomic spectrophotometric absorbance. The treatments on tumor and normal cells were finally evaluated by LM and TM microscopy. Tumor cell death in the case of 0.5 mu m cisplatin on its own was minimal, while in the presence of 0.5 mu m rMnSOD-Lp-CC, no tumor cells survived. Atomic absorbance analysis showed that rMnSOD-Lp-CC delivered approximately four times more cisplatin into HTB-112 cells than the amount delivered using cisplatin alone. By LM observation, the cells treated with rMnSOD-Lp-CC showed signs of nuclear and cytoplasmic fragmentation, that is, apoptosis induced by the treatment. The therapeutic effect of rMnSOD-Lp-CC on endometrial cancer cells was significant, while on the normal cells it showed only a minimal toxicity. We believe that rMnSOD-Lp deserves to be considered as a molecular carrier to deliver cisplatin directly into tumor cells, thus transforming its antireplicative activity into a specific and selective antitumor agent.