Verteporfin‑photodynamic therapy is effective on gastric cancer cells

Mae,Yukari; Kanda,Tsutomu; Sugihara,Takaaki; Takata,Tomoaki; Kinoshita,Hidehito; Sakaguchi,Takuki; Hasegawa,Takashi; Tarumoto,Ryohei; Edano,Mirai; Kurumi,Hiroki; Ikebuchi,Yuichiro; Kawaguchi,Koichiro; Isomoto,Hajime

doi:10.3892/mco.2020.2081

Verteporfin‑photodynamic therapy is effective on gastric cancer cells

Authors:
- Yukari Mae
- Tsutomu Kanda
- Takaaki Sugihara
- Tomoaki Takata
- Hidehito Kinoshita
- Takuki Sakaguchi
- Takashi Hasegawa
- Ryohei Tarumoto
- Mirai Edano
- Hiroki Kurumi
- Yuichiro Ikebuchi
- Koichiro Kawaguchi
- Hajime Isomoto
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Affiliations: Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8504, Japan
Published online on: June 25, 2020 https://doi.org/10.3892/mco.2020.2081
Article Number: 10

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Abstract

Photodynamic therapy (PDT) induces photochemical reactions, resulting in the destruction of tumor cells via singlet (S1) oxygen production. This cellular destruction occurs specifically in tumor cells, following selective accumulation of a photosensitizer and its excitation by a specific wavelength. Verteporfin (VP) is a second‑generation photosensitizer that is currently being used worldwide in PDT to treat age‑related macular degeneration. In addition, clinical trials with VP‑PDT demonstrated anti‑tumor efficacy and overall safety when used to treat locally advanced pancreatic cancer. In the present study, we examined the anti‑tumor effect of VP‑PDT on gastric cancer (GC) cell lines in vitro to conduct an initial assessment of its potential clinical applicability to this specific type of cancer. We evaluated the viability of MKN45 and MKN74 cancer cell lines after VP‑PDT exposure and calculated the half maximal effective concentration (EC₅₀) values for VP. Apoptosis in VP‑PDT‑exposed GC cells was observed. Furthermore, the EC₅₀ values for a 30‑min treatment with VP (2.5 J/cm² of 660 nm LED light) were 0.61 and 1.21 µM for MKN45 and MKN74, respectively. When VP treatment times were increased, the EC50 values decreased. In conclusion, VP‑PDT may be developed as an effective treatment for GC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017.PubMed/NCBI View Article : Google Scholar
2	Isomoto H, Shikuwa S, Yamaguchi N, Fukuda E, Ikeda K, Nishiyama H, Ohnita K, Mizuta Y, Shiozawa J and Kohno S: Endoscopic submucosal dissection for early gastric cancer: A large-scale feasibility study. Gut. 58:331–336. 2009.PubMed/NCBI View Article : Google Scholar
3	Oinuma T, Nakamura T and Nishiwaki Y: Report on the national survey of photodynamic therapy (PDT) for gastric cancer in Japan (a secondary publication). Laser Ther. 25:87–98. 2016.PubMed/NCBI View Article : Google Scholar
4	Nakamura T and Oinuma T: Usefulness of photodynamic diagnosis and therapy using talaporfin sodium for an advanced-aged patient with inoperable gastric cancer (a secondary publication). Laser Ther. 23:201–210. 2014.PubMed/NCBI View Article : Google Scholar
5	Ethirajan M, Chen Y, Joshi P and Pandey RK: The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem Soc Rev. 40:340–362. 2011.PubMed/NCBI View Article : Google Scholar
6	Brown SB and Melish KJ: Verteporfin: A milestone in opthalmology and photodynamic therapy. Expert Opin Pharmacother. 2:351–361. 2001.PubMed/NCBI View Article : Google Scholar
7	Messmer KJ and Abel SR: Verteporfin for age-related macular degeneration. Ann Pharmacother. 35:1593–1598. 2001.PubMed/NCBI View Article : Google Scholar
8	Huggett MT, Jermyn M, Gillams A, Illing R, Mosse S, Novelli M, Kent E, Bown SG, Hasan T, Pogue BW and Pereira SP: Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer. Br J Cancer. 110:1698–1704. 2014.PubMed/NCBI View Article : Google Scholar
9	Park S, Hong SP, Oh TY, Bang S, Chung JB and Song SY: Paclitaxel augments cytotoxic effect of photodynamic therapy using verteporfin in gastric and bile duct cancer cells. Photochem Photobiol Sci. 7:769–74. 2008.PubMed/NCBI View Article : Google Scholar
10	Shimokawa O, Matsui H, Nagano Y, Kaneko T, Shibahara T, Nakahara A, Hyodo I, Yanaka A, Majima HJ, Nakamura Y and Matsuzaki Y: Neoplastic transformation and induction of H+,K+ -adenosine triphosphatase by N-methyl-N'-nitro-N-nitrosoguanidine in the gastric epithelial RGM-1 cell line. In Vitro Cell Dev Biol Anim. 44:26–30. 2008.PubMed/NCBI View Article : Google Scholar
11	Nanashima A, Isomoto H, Abo T, Nonaka T, Morisaki T, Arai J, Takagi K, Ohnita K, Shoji H, Urabe S, et al: How to access photodynamic therapy for bile duct carcinoma. Ann Transl Med. 2(23)2014.PubMed/NCBI View Article : Google Scholar
12	Yang MY, Chang CJ and Chen LY: Blue light induced reactive oxygen species from flavin mononucleotide and flavin adenine dinucleotide on lethality of HeLa cells. J Photochem Photobiol. 173:325–332. 2017.PubMed/NCBI View Article : Google Scholar
13	Celli JP, Solban N, Liang A, Pereira SP and Hasan T: Verteporfin-based photodynamic therapy overcomes gemcitabine insensitivity in a panel of pancreatic cancer cell lines. Lasers Surg Med. 43:565–574. 2011.PubMed/NCBI View Article : Google Scholar
14	Katarzyna B, Moujahed A, Marmalidou A, Horste MM zu, Cichy J, Miller JW, Gragoudas E and Vavvas DG: The clinically used photosensitizer verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation. Exp Eye Res. 124:67–73. 2014.PubMed/NCBI View Article : Google Scholar
15	Kang MH, Jeong GS, Smoot DT, Ashktorab H, Hwang CM, Kim BS, Kim HS and Park YY: Verteporfin inhibits gastric cancer cell growth by suppressing adhesion molecule FAT1. Oncotarget. 8:98887–98897. 2017.PubMed/NCBI View Article : Google Scholar
16	Newman DK: Photodynamic therapy: Current role in the treatment of chorioretinal conditions. Eye. 30:202–210. 2016.PubMed/NCBI View Article : Google Scholar
17	Kanda T, Sugihara T, Takata T, Mae Y, Kinoshita H, Sakaguchi T, Hasegawa T, Kurumi H, Ikebuchi Y, Murakami T and Isomoto H: Low-density lipoprotein receptor expression is involved in the beneficial effect of photodynamic therapy using talaporfin sodium on gastric cancer cells. Oncol Lett. 17:3261–3266. 2019.PubMed/NCBI View Article : Google Scholar
18	Labow RS, Higginson LA, Irvine J, Keaney M, Masters RG, Marquis JF, Meek E, Mussivand T, Walley VM, Logan P, et al: Assessment of the cytotoxicity of the photosensitizing drug BPD verteporfin using human vascular smooth muscle cells in culture. J Cardiovasc Pharmacol. 26:729–736. 1995.PubMed/NCBI
19	Houle JM and Strong HA: Clinical pharmacokinetics of verteporfin. J Clin Pharmacol. 42:547–557. 2002.PubMed/NCBI View Article : Google Scholar