Cisplatin enhances the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy in human head and neck squamous cell carcinoma

Cisplatin enhances the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy in human head and neck squamous cell carcinoma
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DOI:
10.4149/gpb_2013046
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发表时间:
2014-01-01
影响因子:
1.5
通讯作者:
Chung, Phil-Sang
Chung, Phil-Sang
中科院分区:
生物学4区
文献类型:
--
作者:
Ahn, Jin-Chul;Biswas, Raktim;Chung, Phil-Sang

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光动力疗法(PDT)已成为治疗头颈部和其他形式癌症的一种有前途的选择。5-氨基乙酰丙酸(ALA)是PDT中常用的光敏剂之一。它是一种血红素前体,转化为光敏剂原卟啉IX。在本研究中,抗癌药物顺铂(CDDP)和ALA介导的PDT的组合被用来研究细胞毒性在体外以及在体内。人头颈癌细胞AMC-HN 3分别用顺铂和ALA介导的PDT治疗,也联合治疗。已经进行了几种方法,如共聚焦显微镜研究,细胞毒性测定等,以研究原卟啉IX在细胞中的细胞内积累及其在PDT中的有效性,当与化疗药物顺铂(CDDP)联合治疗时。还在肿瘤异种移植模型中研究了治疗功效的组合。与单独治疗相比,发现CDDP和PDT的组合在AMC-HN 3中具有更大的细胞毒性,并且在减少小鼠异种移植物中的肿瘤体积方面也更有效。因此,通过联合治疗,不仅可以提高治疗效果,而且还可以降低药物的剂量。这反过来又可以减少化疗药物的副作用。因此,这项研究可能会导致一个潜在的药物PDT组合,可能是一个有用的治疗方式,人类头颈部癌症。
Photodynamic therapy (PDT) has become a promising option for the treatment of head and neck, and other forms of cancer. 5-Aminolevulinic acid (ALA) is one of the popular photosensitizers used in PDT. It is a heme precursor and is converted to a photosensitizer protoporphyrin IX. In this present study, the combination of anticancer drug cisplatin (CDDP)- and ALA-mediated PDT was used to study the cytotoxicity in vitro as well as in vivo. Human head and neck cancer cells AMC-HN3 were treated with cisplatin- and ALA-mediated PDT individually, and also in combination. Several approaches like confocal microscopic study, cytotoxicity assay, etc have been performed to study the intracellular accumulation of protophorphyrin IX in cells and its effectiveness in PDT, when treated in combination with chemotherapy drug, cisplatin (CDDP). The combination of treatments efficacy was also studied in tumor xenograft model. Compared to the individual treatments, combination of CDDP and PDT was found to be more cytotoxic in AMC-HN3, and also more effective in reducing the tumor volume in mice xenograft. Thus with the combined therapy, not only the efficacy of treatment can be enhanced, but the doses of the drugs can also be lowered. This in turn can reduce the side effects of the chemotherapy drugs. Therefore, this study may lead to a potential drug-PDT combination that may be a useful treatment modality for human head and neck cancer.