Fiorelli Alfonso, Pentimalli Francesca, D'Urso Vittorio, Di Marzo Domenico, Forte Iris Maria, Giordano Antonio, Di Domenico Marina, Accardo Marina, Di Serio Umberto, Santini Mario
Thoracic Surgery Unit, Second University of Naples, Naples, Italy.
INT-CROM, 'Pascale Foundation' National Cancer Institute - Cancer Research Center, Mercogliano, Italy.
Eur J Cardiothorac Surg. 2014 Jun;45(6):993-1000. doi: 10.1093/ejcts/ezt534. Epub 2014 Jan 6.
Povidone-iodine (PVP-I) or Betadine, owing to its antineoplastic activity, is also used as an adjuvant during intra-abdominal or intrathoracic surgery. However, the protocol of PVP-I administration has not been optimized to achieve the best antitumoural efficacy. We aimed to determine the optimal concentration of PVP-I, the time of incubation and the mechanism of cell death by analysing the effect of different doses and time of administration of PVP-I on the cell viability of different mesothelioma cell lines.
Four different cell lines (MET 5A/normal mesothelium; H2052/sarcomatoid mesothelioma; ISTMES2/epithelial mesothelioma; MSTO/biphasic mesothelioma) were incubated with increasing concentrations of diluted PVP-I (0.0001; 0.001; 0.01; 0.1; 1%) for 5, 10, 30, 60 min and 24 h, respectively. Cell viability was determined using cell direct cytotoxicity assay and cell death was determined through flow cytometry assay analysis. The superoxide dismutase activity was assessed functionally through a specific inhibitor to evaluate the mechanism of cell death.
The antiproliferative effect of PVP-I varied largely among different cell lines in a dose- and time-dependent manner. At 0.1% concentration for 10 min of incubation, the percentage of viable cells was 0.5 ± 0.1; 0.8 ± 0.5 and 0% (P < 0.01) for MET5A, ISTMES2 and MSTO, respectively. Conversely, the same concentration did not significantly affect the H2052 cell line which was completely suppressed at a 1% concentration of PVP-I. Double staining of Annexin V and DNA showed that PVP-I induced cell death in all four cell lines via necrosis depending on PVP-I concentration. However, H2052 was found to be more resistant than MSTO, ISTMES2 and MET 5A cells lines. The activity of superoxide dismutase was significantly inhibited in all cell lines.
Our results confirmed the anti-neoplastic activity of PVP-I especially on ISTMES2 and MSTO cell lines. With respect to chemotherapy pleural irrigation, washing with PVP-I is cost-effective and easy. If confirmed by larger studies, our findings suggest that the intrapleural irrigation with PVP-I (0.1% concentration for 10 min) in patients with epithelial or biphasic mesothelioma undergoing cytoreductive surgery might be applied in thoracic surgery practice to prevent neoplastic cell growth.
聚维酮碘(PVP-I)或碘伏,因其抗肿瘤活性,也被用作腹腔或胸腔手术中的辅助剂。然而,PVP-I的给药方案尚未优化以实现最佳抗肿瘤疗效。我们旨在通过分析不同剂量和给药时间的PVP-I对不同间皮瘤细胞系细胞活力的影响,确定PVP-I的最佳浓度、孵育时间和细胞死亡机制。
将四种不同的细胞系(MET 5A/正常间皮;H2052/肉瘤样间皮瘤;ISTMES2/上皮性间皮瘤;MSTO/双向性间皮瘤)分别与浓度递增的稀释PVP-I(0.0001;0.001;0.01;0.1;1%)孵育5、10、30、60分钟和24小时。使用细胞直接细胞毒性试验测定细胞活力,并通过流式细胞术分析测定细胞死亡情况。通过特异性抑制剂功能评估超氧化物歧化酶活性,以评估细胞死亡机制。
PVP-I的抗增殖作用在不同细胞系之间有很大差异,呈剂量和时间依赖性。在0.1%浓度孵育10分钟时,MET5A、ISTMES2和MSTO的活细胞百分比分别为0.5±0.1;0.8±0.5和0%(P<0.01)。相反,相同浓度对H2052细胞系没有显著影响,但在1%浓度的PVP-I下该细胞系被完全抑制。Annexin V和DNA双染显示,PVP-I通过坏死诱导所有四种细胞系的细胞死亡,这取决于PVP-I的浓度。然而,发现H2052比MSTO、ISTMES2和MET 5A细胞系更具抗性。所有细胞系中超氧化物歧化酶的活性均受到显著抑制。
我们的结果证实了PVP-I的抗肿瘤活性,尤其是对ISTMES2和MSTO细胞系。对于化疗性胸腔冲洗,用PVP-I冲洗具有成本效益且操作简便。如果更大规模的研究证实,我们的发现表明,在接受减瘤手术的上皮性或双向性间皮瘤患者中,用PVP-I(0.1%浓度,10分钟)进行胸腔内冲洗可能应用于胸外科实践中以防止肿瘤细胞生长。