Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 968-978
Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.968
Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria
Ying-Qiao Zhang, Qing-Hao Liu, Lu Liu, Peng-Yu Guo, Run-Ze Wang, Zhi-Chang Ba
Ying-Qiao Zhang, Lu Liu, Peng-Yu Guo, Run-Ze Wang, Zhi-Chang Ba, Department of Radiology, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang Province, China
Qing-Hao Liu, Department of Digestive Internal Medicine, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang Province, China
Author contributions: Zhang YQ, Liu QH, and Ba ZC designed the research; Zhang YQ, Liu QH, Liu L, Guo PY, and Wang RZ performed experiments; Zhang YQ, Liu QH, Liu L, Guo PY, and Ba ZC analyzed data; Zhang YQ and Liu QH wrote the paper; Zhang YQ, Liu QH, and Wang RZ constructed the figures and; Ba ZC revised the manuscript; Liu L and Guo PY provided technical assistance; and all authors contributed to the article.
Supported by Haiyan Found of Harbin Medical University Cancer Hospital, No. JJMS2021-03.
Institutional review board statement: These cell lines, as mentioned in the manuscript, are commercially available immortalized cell lines. Importantly, their use in our research does not involve any human subjects, and therefore, the study does not raise any ethical concerns related to human rights, privacy, or similar issues.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Chang Ba, MS, Doctor, Department of Radiology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Harbin 150010, Heilongjiang Province, China. zlyyyxzx@126.com
Received: October 8, 2023
Peer-review started: October 8, 2023
First decision: December 2, 2023
Revised: December 23, 2023
Accepted: January 19, 2024
Article in press: January 19, 2024
Published online: March 15, 2024
Processing time: 156 Days and 8.3 Hours
Abstract
BACKGROUND

Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key.

AIM

To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT.

METHODS

Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4’,6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively.

RESULTS

Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 μmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria.

CONCLUSION

Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Keywords: Photodynamic therapy; Pancreatic cancer; Verteporfin; Mitochondria; Chemotherapy; Gemcitabine

Core Tip: Photodynamic therapy (PDT) for pancreatic cancer (PC) is more effective when the photosensitizer is concentrated in the mitochondria. This study showed that 10 μmol/L verteporfin treatment at various times significantly reduced the survival of human PC cells, but lower concentrations had no discernible results. After gemcitabine treatment, verteporfin was located primarily in the mitochondria. Verteporfin was more prevalent in living than dead cells, and in the latter was found mainly in the mitochondria. This study provides a significant theoretical foundation for using PDT in the comprehensive treatment of PC after neoadjuvant chemotherapy.