冷等离体子体通过 ROS 诱导的细胞凋亡抑制皮肤癌。

Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.

机构信息

Institute of Plasma Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.

University of Science and Technology of China, Hefei, 230026, China.

出版信息

Mol Biol Rep. 2024 Apr 15;51(1):518. doi: 10.1007/s11033-024-09486-6.

DOI:10.1007/s11033-024-09486-6

PMID:38622261

Abstract

BACKGROUND

Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear.

METHODS AND RESULTS

The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis.

CONCLUSIONS

These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

摘要

背景

冷等离体子体（CAP）已广泛应用于生物医学研究，尤其是体外癌症治疗。皮肤鳞状细胞癌（CSCC）是一种源自表皮角质形成细胞的恶性肿瘤。然而，CAP 治疗 CSCC 的机制尚不清楚。

方法和结果

构建了 7,12-二甲基苯并（a）蒽（DMBA）/12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的 CSCC 动物模型。对于 CAP 治疗组，在每次 TPA 应用后，在干燥后每周两次给予 CAP 治疗 3 分钟。用 HE 染色检测各组肿瘤组织的病理状态。通过 Western blot 和 qPCR 评估 PCNA、Bcl-2、Bax、MMP2 和 MMP9 的水平。用 TUNEL 染色检测肿瘤组织中的细胞凋亡。在体内，用 ELISA 检测血清样本中的总 ROS。用 MTT 测定法检测 A431 细胞的活力。用 Western blot 和 qPCR 检测 A431 细胞中 PCNA、Bcl-2、Bax、MMP2 和 MMP9 的水平。用集落形成试验检测 A431 细胞的增殖。用流式细胞术检测 A431 细胞的凋亡比例。Transwell 评估 A431 细胞的迁移和增殖能力。我们发现 CAP 可以诱导皮肤癌细胞凋亡并抑制皮肤癌的进展。通过体外实验，N-乙酰半胱氨酸（NAC）和 CAP 产生的活性氧（ROS）抑制 A431 皮肤癌细胞的增殖和迁移，同时促进细胞凋亡。