Cheng You-Shuang, Peng Yin-Bo, Yao Min, Teng Ji-Ping, Ni Da, Zhu Zhi-Jun, Zhuang Bu-Feng, Yang Zhi-Yin
Department of Cardiothoracic Surgery, No.9 People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China.
Department of Burns and Plastic Surgery, No.9 People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China.
Biochem Biophys Res Commun. 2017 Jun 3;487(3):567-572. doi: 10.1016/j.bbrc.2017.04.089. Epub 2017 Apr 18.
Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.
肺癌是全球癌症死亡的主要原因。小细胞肺癌（SCLC）是一种侵袭性肺癌，其总体5年生存率低于10%。尽管使用顺铂的化疗已被证明对SCLC治疗有效，但传统剂量的顺铂会引起不良副作用。光动力疗法是一种非电离放射疗法，在癌症治疗中越来越多地单独使用或与其他疗法联合使用。在此，我们旨在通过使用体外培养的人SCLC NCI-H446细胞和体内肿瘤异种移植模型，探讨低剂量顺铂联合光动力疗法是否能有效诱导SCLC细胞死亡。我们发现顺铂和光动力疗法在NCI-H446细胞中均表现出剂量依赖性细胞毒性作用。重要的是，低剂量顺铂（1μM）和光动力疗法（1.25J/cm）联合治疗可协同抑制细胞活力和细胞迁移。我们进一步表明，联合治疗在培养的NCI-H446细胞中诱导了更高水平的细胞内活性氧。此外，顺铂和光动力疗法的协同作用在肿瘤异种移植中得到了重现，这表现为TUNEL染色（细胞死亡标志物）更显著增加和肿瘤体积减小。综上所述，我们的研究结果表明，低剂量顺铂联合光动力疗法可能是治疗SCLC患者的一种有效治疗方式。
