G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Prospect 100-Years of Vladivostok, 690022 Vladivostok, Russia.
Department of Biochemistry, Microbiology and Biotechnology, Institute of the World Ocean, Far Eastern Federal University, Campus L, Island Russian, 690920 Vladivostok, Russia.
Molecules. 2022 Jan 19;27(3):628. doi: 10.3390/molecules27030628.
Ginsenoside Rh2 increases the efficacy of doxorubicin (DOX) treatment in murine models of solid and ascites Ehrlich's adenocarcinoma. In a solid tumor model (treatment commencing 7 days after inoculation), DOX + Rh2 co-treatment was significantly more efficacious than DOX alone. If treatment was started 24 h after inoculation, the inhibition of tumor growth of a solid tumor for the DOX + Rh2 co-treatment group was complete. Furthermore, survival in the ascites model was dramatically higher for the DOX + Rh2 co-treatment group than for DOX alone. Mechanisms underlying the combined DOX and Rh2 effects were studied in primary Ehrlich's adenocarcinoma-derived cells and healthy mice's splenocytes. Despite the previously established Rh2 pro-oxidant activity, DOX + Rh2 co-treatment revealed no increase in ROS compared to DOX treatment alone. However, DOX + Rh2 treatment was more effective in suppressing Ehrlich adenocarcinoma cell adhesion than either treatment alone. We hypothesize that the benefits of DOX + Rh2 combination treatment are due to the suppression of tumor cell attachment/invasion that might be effective in preventing metastatic spread of tumor cells. Ginsenoside Rh2 was found to be a modest activator in a Neh2-luc reporter assay, suggesting that Rh2 can activate the Nrf2-driven antioxidant program. Rh2-induced direct activation of Nrf2 might provide additional benefits by minimizing DOX toxicity towards non-cancerous cells.
人参皂苷 Rh2 可提高多柔比星（DOX）治疗实体瘤和腹水型艾氏腹水癌小鼠模型的疗效。在实体瘤模型中（接种后 7 天开始治疗），DOX+Rh2 联合治疗比单独使用 DOX 更有效。如果在接种后 24 小时开始治疗，DOX+Rh2 联合治疗组对实体瘤的生长抑制完全。此外，与单独使用 DOX 相比，DOX+Rh2 联合治疗组在腹水型模型中的存活率显著提高。在原发性艾氏腹水癌细胞和健康小鼠脾细胞中研究了 DOX 和 Rh2 联合作用的机制。尽管之前已经确定 Rh2 具有促氧化剂活性，但与单独使用 DOX 治疗相比，DOX+Rh2 联合治疗并未增加 ROS。然而，与单独使用任何一种药物相比，DOX+Rh2 治疗更有效地抑制了艾氏腺癌细胞的黏附。我们假设 DOX+Rh2 联合治疗的益处是由于抑制了肿瘤细胞的附着/侵袭，这可能有效地防止肿瘤细胞的转移扩散。在 Neh2-luc 报告基因检测中，人参皂苷 Rh2 被发现是一种温和的激活剂，表明 Rh2 可以激活 Nrf2 驱动的抗氧化程序。Rh2 诱导的 Nrf2 直接激活可能通过最小化 DOX 对非癌细胞的毒性提供额外的益处。
