Modulation of EGFR and ROS induced cytochrome c release by combination of photodynamic therapy and carboplatin in human cultured head and neck cancer cells and tumor xenograft in nude mice
Modulation of EGFR and ROS induced cytochrome c release by combination of photodynamic therapy and carboplatin in human cultured head and neck cancer cells and tumor xenograft in nude mice
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DOI：
10.1016/j.jphotobiol.2013.08.001
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发表时间：
2013-11-05
影响因子：
5.4
通讯作者：
Ahn, Jin-Chul
中科院分区：
文献类型：
--
作者：
Hwang, Heejun;Biswas, Raktim;Ahn, Jin-Chul
光动力疗法与不同的治疗方式相结合，已被评估，以研究各种形式的癌症中细胞毒性和细胞凋亡的机制。在本研究中，人头颈癌细胞用radachlorin介导的光动力疗法和化疗药物卡铂单独或联合治疗。研究了几个参数以检查在不同时间间隔的组合疗法的增强的细胞毒性。从通过MTT测定的细胞活力研究中，在组合处理中观察到细胞活力降低22%。通过细胞迁移测定和Hoechst PI染色证实了组合处理的这种增强的活性。活性氧的产生被观察到，并发现高于单独的治疗。发现细胞色素c从线粒体中释放，这也诱导了联合治疗的增强功效。其他蛋白如EGFR和PARP的表达也随处理后孵育时间而调节。在裸鼠模型的肿瘤异种移植研究中，卡铂治疗组的肿瘤体积没有显示出任何明显的变化，而PDT和联合治疗组的肿瘤体积减小。PDT组与联合治疗组在缩小肿瘤体积方面差异无统计学意义，但EGFR的表达在两组间存在差异。还进行了抑制肿瘤生长的组织学研究。因此，本研究可能提供一种通过常规化疗和PDT相结合来对抗头颈癌的途径。(C)2013爱思唯尔有限公司版权所有。
Photodynamic therapy in combination with different treatment modalities has been evaluated to study the mechanism of cellular cytotoxicity and apoptosis in various forms of cancer. In the present study, human head and neck cancer cells were treated with radachlorin mediated photodynamic therapy and the chemotherapy drug, carboplatin singly or in combination. Several parameters were studied to check the enhanced cytotoxicity of combination therapy at different time interval. From the cell viability study by MTT assay, a 22% decrease in cell viability was observed in combination treatment. This enhanced activity of combination treatment was confirmed by cell migration assay and Hoechst PI staining. Generation of reactive oxygen species was observed and found to be higher than that of individual treatments. Cytochrome c was found to be released from mitochondria that also induced the enhance efficacy in combination treatment. The expression of other proteins like EGFR and PARP was also modulated with the time of incubation after treatment. In the tumor xenograft study in nude mouse model, the carboplatin treated group did not show any noticeable changes in tumor volume whereas tumor volume was reduced in PDT and the combination group. Though the difference in the reduction of the tumor size was not significant between PDT and combination group, there was a difference in the expression of EGFR between these two groups. Histologic study of the inhibition in tumor growth was also performed. Therefore, this study may provide an avenue of combating head and neck cancer by a combination of conventional chemotherapy and PDT. (C) 2013 Elsevier B.V. All rights reserved.