Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570, Japan.
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, 362-0806, Japan.
Sci Rep. 2020 Feb 12;10(1):2444. doi: 10.1038/s41598-020-59281-z.
Cancer stem cells (H1299-sdCSCs) were obtained from tumour spheres of H1299 human lung cancer cells. We studied low stiffness, a unique biophysical property of cancer cells, in H1299-sdCSCs and parental H1299. Atomic force microscopy revealed an average Young's modulus value of 1.52 kPa for H1299-sdCSCs, which showed low stiffness compared with that of H1299 cells, with a Young's modulus value of 2.24 kPa. (-)-Epigallocatechin gallate (EGCG) reversed the average Young's modulus value of H1299-sdCSCs to that of H1299 cells. EGCG treatment inhibited tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. AXL receptor tyrosine kinase is highly expressed in H1299-sdCSCs and AXL knockdown with siAXLs significantly reduced tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. An AXL-high population of H1299-sdCSCs was similarly reduced by treatment with EGCG and siAXLs. Transplantation of an AXL-high clone isolated from H1299 cells into SCID/Beige mice induced faster development of bigger tumour than bulk H1299 cells, whereas transplantation of the AXL-low clone yielded no tumours. Oral administration of EGCG and green tea extract (GTE) inhibited tumour growth in mice and reduced p-AXL, ALDH1A1, and SLUG in tumours. Thus, EGCG inhibits the stemness and tumourigenicity of human lung cancer cells by inhibiting AXL.
癌症干细胞（H1299-sdCSCs）是从 H1299 人肺癌细胞的肿瘤球体中获得的。我们研究了低刚性，这是癌细胞的一种独特的生物物理特性，在 H1299-sdCSCs 和亲本 H1299 中。原子力显微镜显示 H1299-sdCSCs 的平均杨氏模量值为 1.52kPa，与 H1299 细胞的杨氏模量值 2.24kPa 相比表现出低刚性。(-)-表没食子儿茶素没食子酸酯（EGCG）将 H1299-sdCSCs 的平均杨氏模量值逆转至 H1299 细胞的水平。EGCG 处理抑制肿瘤球体形成和 ALDH1A1 和 SNAI2（Slug）表达。AXL 受体酪氨酸激酶在 H1299-sdCSCs 中高度表达，siAXLs 敲低 AXL 显著减少肿瘤球体形成和 ALDH1A1 和 SNAI2（Slug）表达。AXL 高表达的 H1299-sdCSCs 也同样被 EGCG 和 siAXLs 处理所减少。从 H1299 细胞中分离的 AXL 高表达克隆移植到 SCID/Beige 小鼠中，比 H1299 细胞的 bulk 移植更快地诱导更大的肿瘤发展，而 AXL 低表达克隆移植则不产生肿瘤。EGCG 和绿茶提取物（GTE）的口服给药抑制了小鼠肿瘤的生长，并降低了肿瘤中的 p-AXL、ALDH1A1 和 SLUG。因此，EGCG 通过抑制 AXL 抑制人肺癌细胞的干性和致瘤性。
