General Hospital of Ningxia Medical University, Yinchuan, 750004 Ningxia, China.
J Immunol Res. 2022 Jul 16;2022:4903333. doi: 10.1155/2022/4903333. eCollection 2022.
This study was designed to observe the treatment effects of flavokawain B (FKB) on gastric cancer both in SGC-7901 cells and nude mice. When SGC-7901 cells were exposed to 10 g/mL FKB, cellular proliferative and apoptotic capacities and cell cycle were detected utilizing CCK-8 and flow cytometry assays. The results showed that FKB treatment induced cell apoptosis and G2/M arrest and suppressed cell proliferation for SGC-7901 cells. Western blot results showed that FKB upregulated proapoptotic proteins as well as downregulated antiapoptotic and cell cycle-related proteins in SGC-7901 cells. SMAD4, TGF-1, and TSPAN12 proteins were tested in FKB-induced SGC-7901 cells. Following exposure to FKB, SMAD4, TGF-1, and TSPAN12 expression was augmented in SGC-7901 cells. si-SMAD4 transfection weakened cell apoptosis and accelerated cell proliferation. Furthermore, FKB reversed the change in apoptotic and cell cycle-related proteins induced by si-SMAD4. A nude mouse tumorigenesis model was constructed, which was treated by FKB. In the nude mouse tumorigenesis model, FKB activated the TSPAN12 expression and TGF-1/SMAD4 pathway. Also, FKB treatment prolonged the survival time of nude mice and lowered tumor weight. iNOS and CD86 expression was significantly enhanced, and Arg-1 and CD206 expression was significantly decreased in THP-1 cells cultured in conditioned media from FKB-treated SGC-7901 cells. Additionally, FKB-treated SGC-7901 cells weakened macrophage migration. Collectively, this evidence suggested that FKB accelerated apoptosis and suppressed the proliferation of gastric cancer cells and attenuated M2 macrophage polarization, thereby exerting an anticancer effect on gastric cancer.
本研究旨在观察 flavokawain B（FKB）对 SGC-7901 细胞和裸鼠胃癌的治疗作用。当 SGC-7901 细胞暴露于 10μg/mL 的 FKB 时，通过 CCK-8 和流式细胞术检测细胞增殖和凋亡能力及细胞周期。结果表明，FKB 处理诱导 SGC-7901 细胞凋亡和 G2/M 期阻滞，抑制细胞增殖。Western blot 结果表明，FKB 上调促凋亡蛋白，下调抗凋亡和细胞周期相关蛋白。检测 FKB 诱导的 SGC-7901 细胞中的 SMAD4、TGF-β1 和 TSPAN12 蛋白。FKB 处理后，SMAD4、TGF-β1 和 TSPAN12 在 SGC-7901 细胞中表达增强。si-SMAD4 转染减弱了细胞凋亡，加速了细胞增殖。此外，FKB 逆转了 si-SMAD4 诱导的凋亡和细胞周期相关蛋白的变化。构建裸鼠肿瘤发生模型，并用 FKB 处理。在裸鼠肿瘤发生模型中，FKB 激活了 TSPAN12 表达和 TGF-β1/SMAD4 通路。此外，FKB 治疗延长了裸鼠的生存时间并降低了肿瘤重量。FKB 处理 SGC-7901 细胞后的条件培养基培养的 THP-1 细胞中 iNOS 和 CD86 的表达显著增强，Arg-1 和 CD206 的表达显著降低。此外，FKB 处理的 SGC-7901 细胞减弱了巨噬细胞迁移。总之，这些证据表明，FKB 加速了胃癌细胞的凋亡和抑制增殖，并减弱了 M2 巨噬细胞极化，从而对胃癌发挥抗癌作用。
