Hypericin-mediated photodynamic therapy of pituitary tumors: preclinical study in a GH4C1 rat tumor model
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Objective Hypericin-mediated photodynamic therapy (PDT) is receiving greater interest as a potential treatment for a variety of tumors and nonmalignant disorders. PDT involves systemic administration of a photosensitizer that selectively accumulates within tumor tissue followed by focal light activation. In the presence of molecular oxygen, a photochemical reaction generates a reactive oxygen species that induces apoptosis in target cells. The purpose of this preclinical study was to evaluate the efficacy of hypericin-mediated PDT for treatment of pituitary adenoma in a rodent model. Methods Wistar-Furth rats were implanted with a pituitary adenoma rat cell line, GH4C1. Tumor masses were allowed to develop over 28 days; rats with tumors of comparable sizes were then assigned to three treatment groups: control (neither hypericin nor light); light only; and hypericin and light. Hypericin was administered in four doses (1 mg/kg) at 28-h intervals prior to light exposure, wherein those rats treated with light were exposed to a light source four hours after the last hypericin dose. Tumor size was measured up to 12 days after treatment. Results Over the short interval examined, hypericin-mediated PDT was not effective against large tumors greater than 1 cm3, but this treatment significantly slowed tumor growth for tumors less than 1 cm3. Histological evaluation and TUNEL assay of the treated tumor identified apoptotic clusters on the periphery of the PDT-treated specimens. Conclusions Hypericin-mediated PDT shows promise in its effectiveness in the treatment of residual small tumor rests.
KeywordsHypericin Photodynamic therapy Pituitary tumor
The authors thank Kristin Kraus for her editorial guidance in preparing this paper and Carolyn Pedone for her direction and assistance with cell culture and tissue preparation.
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