Wang Liang, Xu Lei, Wang Yu
Department of Dermatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Integr Cancer Ther. 2021 Jan-Dec;20:15347354211031646. doi: 10.1177/15347354211031646.
Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.
皮肤鳞状细胞癌（CSCC）是一种起源于表皮或附属器角质形成细胞的恶性肿瘤。中药槐耳在多种恶性肿瘤中具有抗肿瘤活性。关于槐耳在CSCC中的作用知之甚少。在此，我们研究了槐耳在CSCC中的功能。我们用一系列浓度梯度的槐耳处理CSCC细胞系（SCL-1和A431），以检测槐耳对SCL-1和A431细胞的半数最大抑制浓度（IC50）。槐耳对SCL-1和A431细胞生长的IC50分别为6.96和7.57mg/mL。此外，槐耳以剂量依赖性方式降低了SCL-1和A431细胞中CDKN2A和TP53的甲基化水平，并增强了CDKN2A和TP53的表达。在SCL-1和A431细胞中，槐耳处理严重抑制了DNA甲基转移酶DNMT1的表达。DNMT1过表达增强了槐耳处理的SCL-1和A431细胞中CDKN2A和TP53的甲基化水平，并抑制了CDKN2A和TP53的表达。槐耳处理抑制了SCL-1和A431细胞的增殖、迁移和侵袭。然而，抑制CDKN2A或TP53可逆转槐耳处理对CSCC细胞增殖、迁移和侵袭的影响。总之，我们的数据表明，槐耳通过调节CDKN2A和TP53的DNA甲基化来抑制CSCC细胞的增殖、迁移和侵袭，从而减弱CSCC的进展。因此，槐耳提取物可能作为一种治疗CSCC的药物。
