School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, No. 481 Binwen Road, Binjiang District, Hangzhou, 310053, Zhejiang, China.
Department of Clinical Laboratorial Examination, Air Force Hangzhou Special Service Recuperation Center Sanatorium Area 3, Hangzhou, Zhejiang, China.
BMC Complement Med Ther. 2024 Jan 31;24(1):68. doi: 10.1186/s12906-024-04363-y.
Small cell lung cancer (SCLC) is the most malignant lung cancer type. Due to the high rates of metastasis and drug resistance, effective therapeutic strategies remain lacking. Tanshinone IIA (Tan IIA) has been reported to exhibit anti-tumor activity. Therefore, this study investigated the ability and underlying mechanism of Tan IIA to inhibit the metastasis and proliferation of SCLC.
H1688 and H446 cells were treated in vitro with Tan IIA (0, 1, 2 and 4 µM) or LY294002 (10 µM) for 24, 48, 72 h. H1688 and H446 cell migration was evaluated in wound healing and transwell migration assays. RNA-sequencing helped assess gene expression. BALB/c nude mice were injected with H1688 cells and treated with the Tan IIA group (10 mg/kg/day) or a control. Expression of E-cadherin, vimentin and PI3K/Akt signaling pathway proteins in tumors and H1688 was investigated by immunohistochemical analysis and western blot.
Tan IIA inhibited H1688 and H446 cell proliferation without inducing apoptosis and suppressed H1688 and H446 cell migration. E-cadherin expression was increased, while vimentin expression was reduced after administration of Tan IIA. RNA-sequencing revealed that some genes related with the PI3K/Akt signaling pathway were altered using Tan IIA treatment. Furthermore, western blot helped detect PI3K and p-Akt expression was also reduced by Tan IIA treatment. Tan IIA inhibited tumor growth in vivo. Moreover, Tan IIA increased tumoral expression of E-cadherin accompanied by PI3K and p-Akt downregulation.
Tan IIA suppresses SCLC proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway, thereby highlighting the potential of Tan IIA as a new and relatively safe drug candidate to treat SCLC.
小细胞肺癌（SCLC）是最恶性的肺癌类型。由于转移和耐药率高，目前仍缺乏有效的治疗策略。丹参酮 IIA（Tan IIA）已被报道具有抗肿瘤活性。因此，本研究探讨了 Tan IIA 抑制 SCLC 转移和增殖的能力及其潜在机制。
体外采用 Tan IIA（0、1、2 和 4 μM）或 LY294002（10 μM）处理 H1688 和 H446 细胞 24、48 和 72 h。划痕愈合和 Transwell 迁移实验评估 H1688 和 H446 细胞迁移。RNA 测序帮助评估基因表达。BALB/c 裸鼠注射 H1688 细胞，并给予 Tan IIA 组（10 mg/kg/天）或对照组治疗。免疫组化分析和 Western blot 检测肿瘤和 H1688 中 E-钙黏蛋白、波形蛋白和 PI3K/Akt 信号通路蛋白的表达。
Tan IIA 抑制 H1688 和 H446 细胞增殖，不诱导细胞凋亡，并抑制 H1688 和 H446 细胞迁移。Tan IIA 给药后 E-钙黏蛋白表达增加，波形蛋白表达减少。RNA 测序显示 Tan IIA 处理后与 PI3K/Akt 信号通路相关的一些基因发生改变。此外，Western blot 检测到 Tan IIA 处理后 PI3K 和 p-Akt 表达降低。Tan IIA 抑制体内肿瘤生长。此外，Tan IIA 增加肿瘤组织中 E-钙黏蛋白的表达，同时下调 PI3K 和 p-Akt。
Tan IIA 通过抑制 PI3K/Akt 信号通路抑制 SCLC 的增殖和转移，提示 Tan IIA 作为一种新的相对安全的治疗 SCLC 的药物候选物具有潜力。
