RESUMEN
PURPOSE: To investigate the killing effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on human breast cancer MCF7 and MDA-MB-231 cells in vitro. METHODS: MCF7 and MDA-MB-231 breast cancer cells cultured in vitro were incubated with calcitriol (concentration of 10-8M, 10-10 M, 10-12 M, 10-14 M, 10-16 M, 0 M) to determine a proper concentration. The cells were divided into experimental group (calcitriol, HPD group and laser), HPD group (HPD and laser), calcitriol group (calcitriol and laser), blank laser group (laser alone) and blank group (no drugs and laser). Then the cells were preconditioned with calcitriol for 48 hrs and incubated with HPD for 6 hrs. After light exposure with 630 nm laser, the cells' viability and the reactive oxygen species (ROS) were assessed. After 8 hrs, flow cytometry was applied to detect the rate of cell apoptosis. The fluorescence intensity in cells was detected. Furthermore, the expression of porphyrin synthetic enzymes in pretreated breast cancer cells was analyzed. RESULTS: MTT assay showed that the viability of cells in the experimental group was lowest (p<0.05). The ROS intensity of the experimental group was higher (p<0.01). The rate of cell apoptosis was higher in the experimental group (p<0.05), and the fluorescence of the experimental group was higher (p<0.01). Furthermore, mechanistic studies documented that the expression of the porphyrin synthesis enzyme coproporphyrinogen oxidase (CPOX) was increased by calcitriol at the mRNA level. CONCLUSION: This research revealed a simple, non-toxic and highly effective preconditioning regimen to selectively enhance protoporphyrin IX (PpIX) fluorescence and the response of HPD-PDT in breast cancer search. This finding suggests that the combined treatment of breast cancer cells with calcitriol plus HPD may provide an effective and selective therapeutic modality to enhance HPD-induced PpIX fluorescent quality for improving discrimination of tumor tissue and PDT efficacy.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Calcitriol/farmacología , Hematoporfirinas/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Supervivencia Celular/efectos de los fármacos , Coproporfirinógeno Oxidasa/genética , Coproporfirinógeno Oxidasa/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: To investigate the therapeutic effect of surgery, radiotherapy and photodynamic therapy on early glottic carcinoma and prognostic factors. METHODS: Retrospective analysis of 202 cases with early glottic carcinoma (Tis-T2N0M0) underwent surgery (n=152), radiotherapy (n=20) and PDT (n=30) from 2000 to 2013 The KPS score, the disease-free survival (DFS), overall survival (OS), local control (LC), larynx preservation rate, laryngeal function were evaluated. The methods of χ (2)test or Fisher's exact probability method, Kaplan Meier method, log-rank test of Kaplan-Meier method, Cox proportional hazards model were used to analyze the data. RESULTS: There was no statistical significance in OS, DFS and LC among the three groups. The laryngeal function preservation rate of RT group, PDT group and Surgery group were 90%, 86.7% and 65.1% respectively, with the former two groups significantly superior to Surgery group. While there is no statistical significance between RT group and PDT group. Single factor analysis showed that KPS score before treatment, vocal fold mobility limitation and differentiation degree could have an effect on prognosis. Multivariate regression analyses indicated that anterior commissure invasion, T stage and KPS score before treatment were independent adverse prognostic factors for OS. T stage and differentiation degree were adverse prognostic factors for DFS. T stage was also an adverse factor of LC. Thirty-three cases experienced local recurrence or cervical lymph node metastasis. Three groups showed no statistical difference in local recurrence or lymph node metastasis, with twenty-two cases in Surgery group, four in RT group and seven in PDT group. CONCLUSIONS: The therapeutic effect was approximate in surgery group, radiotherapy group and photodynamic group, and all three treatment regimens achieved good clinical effect. Radiotherapy and photodynamic therapy may be the first or very important treatment on early stage glottic squamous cell cancer (Tisâ¼T2N0M0). However only 6 patients underwent PDT for T2 disease, making definitive treatment conclusions for this subgroup unclear.