维生素 D 增强了乳腺癌细胞对光动力疗法和紫杉醇联合治疗的敏感性。
Vitamin D enhances the sensitivity of breast cancer cells to the combination therapy of photodynamic therapy and paclitaxel.
机构信息
Surgical Department, The Third People's Hospital of Hangzhou, China.
Surgical Department, The Third People's Hospital of Hangzhou, China.
出版信息
Tissue Cell. 2022 Aug;77:101815. doi: 10.1016/j.tice.2022.101815. Epub 2022 May 16.
PURPOSE
Given that Vitamin D (VD) has been confirmed to reinforce the toxic effects of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) towards breast cancer, this study was designed to decipher the combined effects of VD, ALA-PDT and paclitaxel (PTX).
METHODS
Thiazolyl blue tetrazolium bromide assay was conducted to gauge the viability of breast cancer cells treated with ALA-PDT and PTX alone or in combination. The cell migration, invasion and apoptosis were measured by wound healing, transwell and flow cytometry assays, respectively. Xenograft tumor models were established and tumor volume and weight were recorded. The expression of Bcl-2, Bax and cleaved caspase-3 in cells and tumor tissues was determined by western blot assay.
RESULTS
Both ALA-PDT and PTX alone inhibited viability in a dose-dependent manner, blocked migration and invasion, boosted apoptosis, down-regulated Bcl-2 expression and upregulated the expression of Bax and cleaved caspase-3 in breast cancer cells. More significant effects on the above-mentioned factors were induced by ALA-PDT and PTX in combination. Moreover, ALA-PDT and PTX in combination also suppressed the growth of xenograft tumors and Bcl-2 expression while promoting the expression of Bax and cleaved caspase-3 in tumors. In contrast, VD had no effect on tumor growth and the expression of Bcl-2, Bax and cleavedcaspase-3, but intensified the combined effects of ALA-PDT and PTX.
CONCLUSION
VD could enhance the therapeutic effects of ALA-PDT combined with PTX on tumor growth and cell apoptosis.
目的
鉴于维生素 D（VD）已被证实可增强 5-氨基酮戊酸基光动力疗法（ALA-PDT）对乳腺癌的毒性作用，本研究旨在破译 VD、ALA-PDT 和紫杉醇（PTX）联合作用的效果。
方法
噻唑蓝溴化四唑比色法检测 ALA-PDT 和 PTX 单独或联合处理的乳腺癌细胞活力。通过划痕愈合、Transwell 和流式细胞术分别检测细胞迁移、侵袭和凋亡。建立异种移植肿瘤模型，记录肿瘤体积和重量。通过 Western blot 检测细胞和肿瘤组织中 Bcl-2、Bax 和 cleaved caspase-3 的表达。
结果
ALA-PDT 和 PTX 单独均呈剂量依赖性抑制细胞活力，阻断迁移和侵袭，促进细胞凋亡，下调 Bcl-2 表达，上调 Bax 和 cleaved caspase-3 的表达。ALA-PDT 和 PTX 联合作用对上述因素的影响更为显著。此外，ALA-PDT 和 PTX 联合还抑制了异种移植瘤的生长和肿瘤中 Bcl-2 的表达，同时促进了 Bax 和 cleaved caspase-3 的表达。相比之下，VD 对肿瘤生长和 Bcl-2、Bax 和 cleaved caspase-3 的表达没有影响，但增强了 ALA-PDT 和 PTX 的联合作用。
结论
VD 可增强 ALA-PDT 联合 PTX 对肿瘤生长和细胞凋亡的治疗效果。
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