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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
CdSe/ZnS quantum dots induce photodynamic effects and cytotoxicity in pancreatic cancer cells
Si-Jia He, Jia Cao, Yong-Sheng Li, Jia-Chun Yang, Min Zhou, Chun-Ying Qu, Yi Zhang, Feng Shen, Ying Chen, Ming-Ming Li, Lei-Ming Xu
Si-Jia He, Jia Cao, Jia-Chun Yang, Min Zhou, Chun-Ying Qu, Yi Zhang, Feng Shen, Ying Chen, Ming-Ming Li, Lei-Ming Xu, Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China
Si-Jia He, the Comprehensive Cancer Center and Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
Yong-Sheng Li, Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China
Author contributions: He SJ and Cao J contributed equally to this study; He SJ, Cao J and Xu LM performed the majority of the experiments; He SJ drafted the manuscript; Cao J and Xu LM designed the study and supervised its implementation; Li YS, Yang JC, Zhou M, Li MM and Qu CY participated in the experiments; Zhang Y, Shen F and Chen Y analyzed the data; all authors made critical revisions and approved the final version to be published.
Supported by the National Natural Science Foundation of China, No. 81472844 and No. 81301826; and Shanghai Municipal Education Commission, No. 14ZZ114.
Institutional review board statement: The study was reviewed and approved by the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Institutional Review Board.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study. The abstract of this paper was presented at AGA Digestive Disease Week as a poster with interim findings, and was published in “Poster Abstracts” in Gastroenterology: http://www.sciencedirect.com/science/article/pii/S0016508515332121.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at leiming.xu@aliyun.com. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lei-Ming Xu, Chief Physician, Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
leiming.xu@aliyun.com
Telephone: +86-21-25078999 Fax: +86-21-25078999
Received: January 18, 2016
Peer-review started: January 19, 2016
First decision: February 18, 2016
Revised: March 4, 2016
Accepted: March 18, 2016
Article in press: March 18, 2016
Published online: June 7, 2016
Processing time: 132 Days and 18.8 Hours
AIM: To investigate the photodynamic effect of CdSe/ZnS quantum dots (QDs) on pancreatic cancer cells and elucidate the probable mechanisms.
METHODS: The pancreatic cancer cell line SW1990 was treated with different concentrations of CdSe/ZnS QDs (0, 0.5, 1.0, 1.5, 2.0, 2.5 μmol/L), with or without illumination. The viability of SW1990 cells was tested using the Cell Counting Kit-8 (CCK-8) assay. The ultrastructural changes of SW1990 cells were observed by transmission electron microscopy. Apoptosis was detected by nuclear staining and flow cytometry (FCM). Reactive oxygen species (ROS) were measured by dichlorofluorescein diacetate via fluorescence microscopy. Expression of Bax, Bcl-2 and caspase-3 was measured by real-time polymerase chain reaction (PCR) and protein immunoblotting 24 h after SW1990 cells were treated with CdSe/ZnS QDs and illuminated.
RESULTS: The CCK-8 assay results showed that both CdSe/ZnS QDs with and without illumination suppressed SW1990 cell proliferation. Cell viability was significantly lower when illuminated or with a longer incubation time and a higher light dose. CdSe/ZnS QDs with illumination caused ultrastructural changes in SW1990 cells, such as organelle degeneration and chromatin condensation and aggregation at the periphery of the nucleus. Fluorescence microscopy and FCM showed that CdSe/ZnS QDs (1.5 μmol/L) with illumination increased SW1990 cell apoptosis (53.2%) and ROS generation compared with no illumination. Real-time PCR showed that expression of Bax and caspase-3 was upregulated and Bcl-2 was downregulated. Immunoblotting results were consistent with real-time PCR results. Inhibition of ROS and apoptosis both attenuated QD-photodynamic-therapy-induced cell death.
CONCLUSION: CdSe/ZnS QDs can be used as a photosensitizer to inhibit SW1990 cell proliferation through ROS generation and apoptotic protein expression regulation.
Core tip: This study showed that quantum dots (QDs) may be a potential photosensitizer for photodynamic therapy (PDT) to treat pancreatic cancer by inhibiting SW1990 cell proliferation and inducing apoptosis through reactive oxygen species (ROS) generation. QD-PDT may induce apoptosis through ROS-, caspase-3-mediated apoptotic pathways, with upregulation of apoptosis signaling molecules such as Bax and downregulation of Bcl-2. These findings provide a new application for PDT in pancreatic cancer. However, more preclinical and clinical trials should be undertaken before further clinical application.
