Cell lines

RAW 264.7 cells

Preparation Method

RAW 264.7 cells were pretreated with 2 μM verteporfin for 2 h, then stimulated with LPS (1 μg/ml) for 22 h.

Reaction Conditions

2 μM; 2 h

Applications

When RAW 264.7 cells were treated with 2 μM verteporfin, GCSF, IL-6, CCL2, MCP-5, CCL5, and TNF-α were significantly inhibited compared with cells treated with LPS alone.

Animal models

C57BL/6 mice

Preparation Method

Lewis lung carcinoma cells (LLCs, 5 x 10⁵in 100 μl phosphate-buffered saline) were inoculated subcutaneously into C57BL/6 mice (male, 8–12 weeks) in both flanks. Five days after inoculation, mice were randomly divided into 4 groups and treated with vehicle, BMN 673 0.33 mg/Kg daily (oral gavage), verteporfin 30 mg/kg daily (intraperitoneal injection) and the combination of BMN 673 with verteporfin for 16 days. Tumors size were measured every 2 days by digital calipers to determine tumor volume using the formula [length/2] × [width2].

Dosage form

30 mg/kg; i.p.

Applications

Verteporfin treatment led to marked decreases in PD-L1 expression and increases in CD8 T cells especially in the combinatorial group of vereporfin and BMN 673.

Verteporfin is a potent inhibitor of PD-L1 expression used for treatment in the age-related macular degeneration , port-wine stain birthmarks and cancer.^[1]

In vitro experiment it shown that at 1μM versus 0.5 μM concentrations of verteporfin, it was sufficient to decrease PD-L1 expression in ATG5 depleted cells.^[1]In vitro, at very low concentrations of verteporfin (0.1–0.2 μm) , verteporfin induced significant cell death in GSCs. However, 0.5 μm verteporfin had no effect on the cell death in differentiated GSCs, IMR90, rat NSCs or mouse astrocytes.^[2]In vitro efficacy test it indicated treatment with 4, 8 and 12 μM verteporfin decreased significantly the expression levels of YAP, AXL and CYR61 mRNA in MCF-7, BT-474 and BT-549 cells. And verteporfin also downregulated the mRNA expression of CTGF in BT-474 and BT-549 cells.^[3]Treatment with 0.5, 1, 2, and 5 μM verteporfin inhibited the viability of HeLa cells and had no obvious effect on H8 cells.^[4]

In vivo study it demonstrated that treatment with 2 mg.kg-1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. However, mice were treated 8 mg.kg-1 nanostructured lipid carriers-verteporfin intravenously laser light exposure of tumors significantly inhibited tumor growth without visible toxicity.^[5]In vivo, 2 mg/kg verteporfin infusion alone resulted in nitric oxide and malonyldialdehyde level increments in the retina.^[6]

References:
[1].Liang J, et al. Verteporfin Inhibits PD-L1 through Autophagy and the STAT1-IRF1-TRIM28 Signaling Axis, Exerting Antitumor Efficacy. Cancer Immunol Res. 2020 Jul;8(7):952-965. Kuramoto K, Yamamoto M, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C, Okada M.
[2].Kuramoto K, et al. Verteporfin inhibits oxidative phosphorylation and induces cell death specifically in glioma stem cells. FEBS J. 2020 May;287(10):2023-2036.
[3].Wei C, Li X. Verteporfin inhibits cell proliferation and induces apoptosis in different subtypes of breast cancer cell lines without light activation. BMC Cancer. 2020 Oct 29;20(1):1042.
[4].Yin L, Chen G. Verteporfin Promotes the Apoptosis and Inhibits the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Downregulating SULT2B1 Expression. Med Sci Monit. 2020 Oct 20;26:e926780.
[5].Michy T, et al. Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo. Cancers (Basel). 2019 Nov 8;11(11):1760.
[6].Turkuoglu P, et al. Retinal nitric oxide and malonyldialdehyde levels following photodynamic therapy. Indian J Ophthalmol. 2011 Jan-Feb;59(1):5-8.