Adriamycin enhanced in vitro and in vivo photodynamic therapy of mesothelioma

Abstract

The ability of Adriamycin (AD) to enhance the known in vitro and in vivo tumoricidal effects of photodynamic therapy (PDT) on the H-MESO-1 human malignant mesothelioma cell line was investigated. In vitro cytotoxicity was determined by incubating H-MESO-1 cells in microtiter plates (2 × 10 5 cells/well, 6 wells/group) with the photosensitizer Photofrin II (PF) and varying concentrations of AD (0, 2.5, 5.0, and 10.0 μm/ml) for 24 hr followed by exposure to gold vapor laser light (GVL) at a fluence of 6000 J/M 2. [ 3H]Thymidine (1 μCi) was added to each well 24 hr after treatment. Cells were harvested and counted for thymidine incorporation 24 hr later. PDT alone resulted in a decrease in thymidine incorporation of 23% while the addition of AD to PDT at AD concentrations of 2.5, 5.0, and 10.0 μg/ml resulted in decreases of 62, 85, and 69%, respectively ( P = 0.005) as compared to untreated controls. H-MESO-1 tumor bearing nude mice ( n = 5) were injected ip with PF (5 mg/kg) and AD (5 mg/kg) 24 hr prior to illumination of the tumor site with GVL (120 J/cm 2). Control groups ( n = 5) received PDT, AD, and/or GVL alone. Tumor surface area was measured as the product of the greatest perpendicular dimensions every 5 days for 30 days. Administration of PDT without AD resulted in a decrease in tumor surface area of 50% on Day 10 with regrowth of tumor by Day 30 while AD alone with or without GVL had no impact on tumor growth. The addition of AD to PDT resulted in 100% tumor necrosis on Day 5 with no tumor regrowth. The use of PDT led to a significant ( P < 0.02) decrease in tumor area while the addition of AD resulted in a more rapid, intense, and prolonged response. The addition of AD to PDT appears to result in greater tumor killing both in vitro and in vivo than does PDT alone.