Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Department of Oral and Maxillofacial surgery, Medical University of Vienna, Vienna, Austria.
Wien Klin Wochenschr. 2021 Jan;133(1-2):26-31. doi: 10.1007/s00508-020-01729-3. Epub 2020 Sep 2.
The selective PI3K (Phosphatidylinositol 3-kinase) inhibitor HS-173 has anticancer activity in non-small cell lung cancer and pancreatic cancer cells. Of all head and neck squamous cell carcinomas (HNSCC) 20% harbor specific mutations in the genome. The aim of this study was to investigate the effect of HS-173 on HNSCC cell lines.
The cell lines SCC25, CAL27 and FaDu were incubated with HS-173. Its antiproliferative effect was determined using the CCK‑8 cell proliferation assay. Combined incubation with cisplatin was performed and combination index analysis was conducted. To investigate its effect on radiotherapy, cells were irradiated with 2, 4, 6 and 8 Gy, respectively. Synergistic effects of radiation and HS-173 were measured by proliferation assays and clonogenic survival.
The use of HS-173 induced significant reduction of cell proliferation across all cell lines. Most interestingly, it showed a synergistic effect with cisplatin treatment. Clonogenic survival revealed a radiosensitizing effect in CAL27 and FaDu cells. The HS-173 caused significant induction of apoptosis in SCC25 and FaDu cells.
The selective PI3K inhibitor HS-173 is a potent chemosensitizing and also radiosensitizing drug in treatment of HNSCC cell lines and could be an effective treatment in PI3K-mutated HNSCC.
选择性 PI3K(磷脂酰肌醇 3-激酶)抑制剂 HS-173 在非小细胞肺癌和胰腺癌细胞中具有抗癌活性。所有头颈部鳞状细胞癌(HNSCC)中有 20%的肿瘤在基因组中存在特定的突变。本研究旨在研究 HS-173 对 HNSCC 细胞系的影响。
将 SCC25、CAL27 和 FaDu 细胞系与 HS-173 孵育。使用 CCK-8 细胞增殖测定法测定其抗增殖作用。进行与顺铂的联合孵育,并进行组合指数分析。为了研究其对放疗的影响,分别用 2、4、6 和 8 Gy 对细胞进行照射。通过增殖测定和克隆形成生存实验来测量辐射和 HS-173 的协同作用。
使用 HS-173 诱导所有细胞系的细胞增殖显著减少。最有趣的是,它与顺铂治疗显示出协同作用。集落形成生存实验揭示了 CAL27 和 FaDu 细胞的放射增敏作用。HS-173 导致 SCC25 和 FaDu 细胞显著诱导细胞凋亡。
选择性 PI3K 抑制剂 HS-173 是一种有效的治疗 HNSCC 细胞系的化疗增敏剂,也是放射增敏剂,并且可能是 PI3K 突变型 HNSCC 的有效治疗方法。