Nanjing University of Chinese Medicine, Nanjing, China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Clin Exp Pharmacol Physiol. 2022 Dec;49(12):1270-1280. doi: 10.1111/1440-1681.13708. Epub 2022 Aug 30.
Gastric cancer (GC) is one of the most prevalent malignancies of the digestive tract. Ginsenoside Rh1 was reported to exert effects on GC. The current study set out to explore the mechanism underlying Ginsenoside Rh1 effects on GC. With oxaliplatin (OXA) serving as the positive control, human GC cells AGS were treated with 0, 10, 25, 50, 74, or 100 μM of ginsenoside Rh1 for 48 h. Proliferation, migration, invasion, and apoptosis were subsequently assessed by means of MTT, scratch test, Transwell, and TUNEL, respectively. AGS cells were further jointly treated with Rh1 and the TGF-β/Smad pathway activator Kartogenin, followed by detection of TGF-β/Smad pathway effects on AGS biological behaviours. Moreover, TGF-β/Smad pathway activation was detected with a Western blot assay. Furthermore, xenograft tumour models were established and tumour growth was recorded. Ki-67 expression patterns and apoptosis were detected with immunohistochemistry and TUNEL, respectively. In vitro, Ginsenoside Rh1 repressed AGS cell proliferation, migration, and invasion, and further promoted apoptosis, with a concentration of 50 μM Rh1 exerting the equivalent effects as OXA. In vivo, Ginsenoside Rh1 inhibited GC proliferation and induced tumour cell apoptosis. Mechanistically, Ginsenoside Rh1 reduced TGF-β1 and TGF-β2 levels and Smad2 and Smad3 phosphorylation levels. Collectively, our findings highlighted that ginsenoside Rh1 inhibited GC cell growth and tumour growth in xenograft tumour models via inhibition of the TGF-β/Smad pathway.
胃癌（GC）是最常见的消化道恶性肿瘤之一。有报道称人参皂苷 Rh1 对 GC 有作用。本研究旨在探讨人参皂苷 Rh1 对 GC 作用的机制。以奥沙利铂（OXA）为阳性对照，用 0、10、25、50、74 或 100μM 人参皂苷 Rh1 处理人 GC 细胞 AGS 48h。随后分别采用 MTT、划痕试验、Transwell 和 TUNEL 检测细胞增殖、迁移、侵袭和凋亡。AGS 细胞进一步与 Rh1 和 TGF-β/Smad 通路激活剂 Kartogenin 联合处理，然后检测 TGF-β/Smad 通路对 AGS 生物学行为的影响。此外，采用 Western blot 检测 TGF-β/Smad 通路的激活。进一步建立异种移植瘤模型并记录肿瘤生长。采用免疫组化和 TUNEL 检测 Ki-67 表达模式和细胞凋亡。在体外，人参皂苷 Rh1 抑制 AGS 细胞增殖、迁移和侵袭，进一步促进细胞凋亡，50μM Rh1 的作用与 OXA 相当。在体内，人参皂苷 Rh1 抑制 GC 增殖并诱导肿瘤细胞凋亡。机制上，人参皂苷 Rh1 降低了 TGF-β1 和 TGF-β2 水平以及 Smad2 和 Smad3 的磷酸化水平。总之，我们的研究结果表明，人参皂苷 Rh1 通过抑制 TGF-β/Smad 通路抑制 GC 细胞生长和异种移植瘤模型中的肿瘤生长。
