Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells

Abstract

Abstract. to identify a possible new treatment modality for malignant pleural mesothelioma (MPM), we examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDt) using the photosensitizer nPe6, enhanced the antitumor effect in both in vitro and in vivo models. We also investigated preclinical treatment schedules. four human malignant mesothelioma cell lines (MSto-211H, H2052, H2452 and H28) were assayed using the WSt assay after treatment with pemetrexed and nPe6-PDt. the treatment schedule for the combination treatment was examined using nude mice. Pemetrexed pre-treatment enhanced the lethal effect of nPe6-PDt in the four malignant mesothelioma cell lines, but nPe6-PDt followed by pemetrexed treatment did not enhance cell lethality in the in vitro assay. Pemetrexed pre-treatment did not enhance the intracellular accumulation of nPe6, which is one of the determinants of the antitumor effect of PDt. in nude mice injected with MSto-211H cells and then treated using a combination of pemetrexed and nPe6-PDt (10 mg/kg nPe6, 10 j/cm 2 laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pre-treatment value after 14 days. Pemetrexed treatment followed by nPe6-PDt resulted in an 80% reduction in the tumor size and inhibited re-growth. nPe6-PDt followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re-growth. nPe6-PDt induced the expression of thymidylate synthase (tS), which confers resistance to pemetrexed, and nPe6-PDt followed by pemetrexed treatment did not enhance the treatment outcome in vivo. in conclusion, combination treatment, consisting of pemetrexed followed by nPe6-PDt, should be further investigated as a new treatment modality for MPM. in the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with MPM.

The YAP1 Signaling Inhibitors, Verteporfin and CA3, Suppress the Mesothelioma Cancer Stem Cell Phenotype

“…Photosensitizers, like verteporfin, have been used to treat mesothelioma (37,38). In this procedure, the tumor is surgically removed and the body cavity is bathed in photosensitizer which is then activated by laser irradiation (39)(40)(41)(42).…”

Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression

“…no. 35-5800; Zymed; Thermo Fisher Scientific Inc.) (33,35). After rinsing with PBS containing 0.1% (v/v) Triton X-100, the membranes were incubated with goat anti-rat immunoglobulin-G (IgG)-conjugated horseradish peroxidase (HRP) (1:10,000 dilution; cat.…”

Cell Death Pathways Associated with Photodynamic Therapy: An Update

“…In this context, it should be noted that most chemotherapy protocols involve use of multiple drugs, with a view toward minimizing adverse clinical reactions while providing additive or synergistic tumor kill. PDT has also been used in conjunction with chemotherapy with some success , and PDT may even interact with lesions produced by ionizing radiation to change the mechanism of cell death from one typical of radiation to one more typical of PDT . The nature of this synergy is not yet clear.…”