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.