A Molecular Carrier to Transport and Deliver Cisplatin into Endometrial Cancer Cells

被引:7
作者
Borrelli, Antonella [1 ]
Schiattarella, Antonietta [1 ]
Musella, Alessandra [1 ]
Mancini, Roberto [1 ]
Capasso, Clemente [2 ]
De Luca, Viviana [2 ]
Carginale, Vincenzo [2 ]
Sanseverino, Marina [3 ]
Tornesello, Anna Lucia [3 ]
Gori, Enrico [4 ]
Pica, Alessandra [5 ]
Di Santi, Annalisa [5 ]
Basile, Filomena [5 ]
Iacobellis, Francesca
Colacurci, Nicola [6 ]
Cobellis, Luigi [6 ]
Mancini, Aldo [1 ]
机构
[1] Naples Pascale Fdn, NCI, Naples, Italy
[2] CNR, Inst Prot Biochem, I-80125 Naples, Italy
[3] INBIOS Srl, Naples, Italy
[4] Univ Udine, Dept Stat, I-33100 Udine, Italy
[5] Univ Naples Federico II, Dept Biol Sci, Naples, Italy
[6] Univ Naples 2, Dept Gynecol Obstet & Reprod, Naples, Italy
关键词
cisplatin; leader peptide; MITOCHONDRIAL DRUG-DELIVERY; GYNECOLOGIC-ONCOLOGY-GROUP; LIPOSOMAL DOXORUBICIN; PHASE-II; CARCINOMA; TRIAL; CHEMOTHERAPY; RECURRENT; THERAPY; RADIOTHERAPY;
D O I
10.1111/j.1747-0285.2012.01337.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:9 / 16
页数:8
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