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宫颈癌细胞(HeLa)对使用锌酞菁光敏剂的光动力疗法的反应。

Cervical cancer cells (HeLa) response to photodynamic therapy using a zinc phthalocyanine photosensitizer.

作者信息

Hodgkinson Natasha, Kruger Cherie Ann, Mokwena Mpho, Abrahamse Heidi

机构信息

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa.

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa.

出版信息

J Photochem Photobiol B. 2017 Dec;177:32-38. doi: 10.1016/j.jphotobiol.2017.10.004. Epub 2017 Oct 4.

DOI:10.1016/j.jphotobiol.2017.10.004
PMID:29045918
Abstract

Cervical cancer is the most common gynecological malignancy worldwide, and the leading cause of cancer related deaths among females. Conventional treatment for early cervical cancer is radical hysterectomy. In locally advanced cancer the treatment of choice is concurrent chemo radiation. Although such treatment methods show promise, they do have adverse side effects. To minimize these effects, as well as prevent cancer re-occurrence, new treatment methods are being investigated. Photodynamic therapy (PDT) involves the selective uptake of a photosensitizer (PS) by cancer cells, illumination with light of an appropriate wavelength that triggers a photochemical reaction leading to the generation of reactive oxygen and subsequent tumor regression. The effect of PDT on a cervical cancer cell line (HeLa) was assessed by exposing cultured cells to a sulphonated zinc phthalocyanine PS (ZnPcS) and irradiating the cells using a 673nm diode laser. The effects were measured using the Trypan blue viability assay, adenosine triphosphate assay (ATP) luminescence assay for proliferation, Lactate Dehydrogenase (LDH) membrane integrity cytotoxicity assay, and fluorescent microscopy to assess PS cellular localization and nuclear damage. Fluorescent microscopy revealed localization of the PS in the cytoplasm and perinuclear region of HeLa cells. PDT treated cellular responses showed dose dependent structural changes, with decreased cell viability and proliferation, as well as considerable membrane damage. Hoechst stained cells also revealed DNA damage in PDT treated cells. The final findings from this study suggest that ZnPcS is a promising PS for the PDT treatment of cervical cancer in vitro, where a significant 85% cellular cytotoxicity with only 25% cellular viability was noted in cells which received 1μM ZnPcS when an 8J/cm fluence was applied.

摘要

宫颈癌是全球最常见的妇科恶性肿瘤,也是女性癌症相关死亡的主要原因。早期宫颈癌的传统治疗方法是根治性子宫切除术。对于局部晚期癌症,首选治疗方法是同步放化疗。尽管这些治疗方法显示出前景,但它们确实有不良副作用。为了尽量减少这些影响以及预防癌症复发,正在研究新的治疗方法。光动力疗法(PDT)涉及癌细胞选择性摄取光敏剂(PS),用适当波长的光照射,引发光化学反应,导致活性氧生成及随后的肿瘤消退。通过将培养的细胞暴露于磺化锌酞菁PS(ZnPcS)并用673nm二极管激光照射细胞,评估PDT对宫颈癌细胞系(HeLa)的作用。使用台盼蓝活力测定法、用于增殖的三磷酸腺苷测定法(ATP)发光测定法、乳酸脱氢酶(LDH)膜完整性细胞毒性测定法以及荧光显微镜来评估PS细胞定位和核损伤,测量其效果。荧光显微镜显示PS定位于HeLa细胞的细胞质和核周区域。PDT处理后的细胞反应显示出剂量依赖性的结构变化,细胞活力和增殖降低,以及相当程度的膜损伤。Hoechst染色的细胞也显示出PDT处理后细胞的DNA损伤。这项研究的最终结果表明,ZnPcS是一种有前景的用于体外PDT治疗宫颈癌的PS,当施加8J/cm的能量密度时,在接受1μM ZnPcS的细胞中,观察到显著的85%细胞毒性,而细胞活力仅为25%。

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