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瘤内光动力疗法通过半胱天冬酶 3 和颗粒酶 B 诱导基底细胞癌和鲍恩病细胞凋亡。

Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

机构信息

Department of Dermatology, University Hospital of Heraklion, Heraklion, Greece.

Department of Pathology, University Hospital of Crete, Heraklion, Greece.

出版信息

J Eur Acad Dermatol Venereol. 2023 Jul;37(7):1311-1317. doi: 10.1111/jdv.19050. Epub 2023 Mar 23.

DOI:10.1111/jdv.19050
PMID:36924124
Abstract

BACKGROUND

Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor.

OBJECTIVES

To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease).

METHODS

Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK.

RESULTS

Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT.

CONCLUSION

Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

摘要

背景

光动力疗法(PDT)用于治疗皮肤癌。它可能通过直接和间接途径诱导细胞死亡,包括细胞凋亡、炎症和某些免疫机制,渗透深度是一个潜在的修饰因子。

目的

研究基底细胞癌(BCC)和表皮内鳞状细胞癌(鲍文病)的腔内 PDT 中细胞凋亡的途径。

方法

16 例浅表或结节性 BCC 和鲍文病患者接受腔内氨基酮戊酸-PDT 治疗。在 PDT 后 24 小时内,取基线和活检,并用免疫组织化学检查细胞凋亡标志物的表达,如参与内在凋亡途径的半胱氨酸蛋白酶 3(caspase 3)、无半胱氨酸蛋白酶依赖性凋亡介质颗粒酶 B 以及促凋亡标志物 BAX 和 BAK。

结果

TUNEL 染色的凋亡细胞在 PDT 后 24 小时有统计学意义的染色(BCC 和鲍文病病变均为 p<0.01)。caspase 3(BCC 为 p<0.01,鲍文病为 p<0.05)和颗粒酶 B(BCC 为 p<0.01,鲍文病为 p<0.01)在 PDT 后 24 小时明显增加。与基线相比,鲍文病病变在 PDT 后 24 小时 Bax 的表达明显增加,而 Bak 在 BCC 和鲍文病中均在基线和 PDT 后 24 小时上调。

结论

腔内 PDT 通过涉及颗粒酶 B 的共同和替代凋亡途径诱导 BCC 和鲍文病的细胞凋亡。促凋亡因子 Bak 在 BCC 和鲍文病中以及 Bax 在鲍文病中似乎在 24 小时内通过腔内 PDT 增加。

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