Modulating mitochondrial morphology enhances antitumor effect of 5-ALA-mediated photodynamic therapy both in vitro and in vivo
Hongyou Zhao, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China; Department of Genetics, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Rong Yin, Department of Dermatology, the Second Hospital, Shanxi Medical University, Taiyuan 030001,PR China.
Ying Wang, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Yuan-Hao Lee, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
Ting Luo, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Jiaying Zhang, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Haixia Qiu, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Stephen Ambrose, College of Medicine, University of South Alabama, Mobile 36688, USA.
Lijie Wang, Department of Oncology, Chinese PLA General Hospital, Beijing 100853, PR China.
Jie Ren, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Jie Yao, Department of Oncology, Chinese PLA General Hospital, Beijing 100853, PR China.
Defu Chen, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Yucheng Wang, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Zhipin Liang, Department of Genetics, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Jie Zhen, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Sumin Wu, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Zulin Ye, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Jing Zeng, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Naiyan Huang, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China.
Ying Gu, Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, PR China. Electronic address: guyinglaser301@163.com.
Abstract
5-aminolevulinic acid mediated PDT (5-ALA-PDT) is an approved therapeutic procedure for treating carcinomas of the cervix. However, when employed as a monotherapy, 5-ALA-PDT could not produce satisfactory results toward large and deep tumors. Therefore, developing a method to improve the efficacy of 5-ALA-PDT becomes important. In this study, we demonstrate an enhanced antitumor effect of 5-ALA-PDT by the modulation of mitochondrial morphology. The mitochondria in the cells were regulated into tubular mitochondria or fragmented mitochondria through over expression of Drp1 or Mfn2. Then these cells were treated with identical dose of 5-ALA-PDT. Our results suggest that HeLa cells predominantly containing fragmented mitochondria were more sensitive to 5-ALA-PDT than the cells predominantly containing tubular mitochondria. The morphology of mitochondria changed as the cell cycle progressed, with tubular mitochondria predominantly exhibited in the S phase and uniformly fragmented mitochondria predominantly displayed in the M phase. Paclitaxel significantly increased the population of M-phase cells, while 5-fluorouracil significantly increased the population of S-phase cells in xenograft tumors. Furthermore, low-dose paclitaxel significantly increased the antitumor effects of PDT. However, 5-fluorouracil didn't improve the antitumor effects of PDT. These results demonstrated an enhanced antitumor effect of 5-ALA-PDT from the modulation of mitochondrial morphology. We anticipate that our results will provide an insight for selecting potential chemotherapeutic agents to combine with PDT for tumor treatment.
