Int J Biol Sci 2019; 15(1):12-23. doi:10.7150/ijbs.27156
Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells
1. Department of Pharmacy, Changhai Hospital, The Second Military Medical University, Shanghai, China
2. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
3. Department of Information, Changzheng Hospital, The Second Military Medical University, Shanghai, China
4. Department of Pharmacy, The Second Hospital of Anhui Medical University, Hefei, China
5. GCP Office, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
* These authors contributed equally to this work.
To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect.
Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-Ⅱ). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells.
Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.
Keywords: sinoporphyin sodium, photodynamic therapy, colorectal cancer, apoptosis, autophagy, chloroquine
Zhu B, Li S, Yu L, Hu W, Sheng D, Hou J, Zhao N, Hou X, Wu Y, Han Z, Wei L, Zhang L. Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells. Int J Biol Sci 2019; 15(1):12-23. doi:10.7150/ijbs.27156. Available from http://www.ijbs.com/v15p0012.htm