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阿霉素与磺化锌酞菁介导的光动力疗法对MCF-7乳腺癌细胞的体外联合效应

In vitro combined effect of Doxorubicin and sulfonated zinc Phthalocyanine-mediated photodynamic therapy on MCF-7 breast cancer cells.

作者信息

Aniogo Eric Chekwube, George Blassan Plackal Adimuriyil, Abrahamse Heidi

机构信息

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa.

出版信息

Tumour Biol. 2017 Oct;39(10):1010428317727278. doi: 10.1177/1010428317727278.

DOI:10.1177/1010428317727278
PMID:29022483
Abstract

Doxorubicin is a broad-spectrum antibiotic and anticancer drug used to treat a variety of human malignancies like breast cancer and leukaemia. Unfortunately, a dose-dependent side effect of this drug is common, representing a major obstacle to its use despite its therapeutic efficacy. Photodynamic therapy is an emerging non-invasive potential adjuvant for conventional cancer treatment. In an attempt to circumvent the dose-limiting effect of doxorubicin, this study aimed to investigate cellular anticancer activity of doxorubicin and sulfonated zinc phthalocyanine-mediated photodynamic therapy on MCF-7 cells alone and in combination. Furthermore, we investigated the cell death pathway resulting from the combination treatment. MCF-7 cells were incubated with 0.5 µM concentration of doxorubicin for 20 h, afterwards, various concentrations of sulfonated zinc phthalocyanine were added and incubated for 4 h. Cells were irradiated using a 681.5 nm diode laser at 4.53 mW/cm for 18 min 24 s (5 J/cm). Cell viability and proliferation were measured using trypan blue assay and homogeneous adenosine triphosphate quantitation assay, respectively, while qualitative changes in cellular morphology were observed under inverted light microscopy. Cellular DNA damage was assessed under fluorescent microscopy and Annexin V/propidium iodide stain was used to investigate the cell death pathway. Findings from this study shown that combined treatment with doxorubicin and photodynamic therapy was more effective in inhibiting the proliferation and growth of MCF-7 cells. Overall, the results indicate that combination of smaller dose of doxorubicin with photodynamic therapy is a promising combined treatment strategy for breast carcinoma. However, this combination warrants further investigation.

摘要

阿霉素是一种广谱抗生素和抗癌药物,用于治疗多种人类恶性肿瘤,如乳腺癌和白血病。不幸的是,这种药物常见剂量依赖性副作用,尽管具有治疗效果,但这仍是其应用的主要障碍。光动力疗法是一种新兴的用于传统癌症治疗的非侵入性潜在辅助疗法。为了规避阿霉素的剂量限制效应,本研究旨在单独及联合研究阿霉素与磺化锌酞菁介导的光动力疗法对MCF-7细胞的细胞抗癌活性。此外,我们研究了联合治疗导致的细胞死亡途径。将MCF-7细胞与0.5μM浓度的阿霉素孵育20小时,之后加入不同浓度的磺化锌酞菁并孵育4小时。使用681.5nm二极管激光以4.53mW/cm的功率照射细胞18分钟24秒(5J/cm)。分别使用台盼蓝测定法和均相三磷酸腺苷定量测定法测量细胞活力和增殖,同时在倒置光学显微镜下观察细胞形态的定性变化。在荧光显微镜下评估细胞DNA损伤,并使用膜联蛋白V/碘化丙啶染色来研究细胞死亡途径。本研究结果表明,阿霉素与光动力疗法联合治疗在抑制MCF-7细胞的增殖和生长方面更有效。总体而言,结果表明小剂量阿霉素与光动力疗法联合是一种有前景的乳腺癌联合治疗策略。然而,这种联合疗法有待进一步研究。

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