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高含量人参二醇(Ginseng Rh2+)抑制非小细胞肺癌的肿瘤生长和转移。

Rh2-enriched Korean ginseng (Ginseng Rh2+) inhibits tumor growth and development of metastasis of non-small cell lung cancer.

机构信息

Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv Sourasky Medical Center, affiliated to Tel-Aviv University, Israel.

出版信息

Food Funct. 2021 Sep 7;12(17):8068-8077. doi: 10.1039/d1fo00643f. Epub 2021 Jul 20.

DOI:10.1039/d1fo00643f
PMID:34286798
Abstract

BACKGROUND AND OBJECTIVE

While there are multiple studies on the anti-tumoral effects of Panax ginseng as active ingredients (one or more ginsenosides derived from the extract) or as a whole plant extract, there is a lack of studies to assess the effects Panax ginseng's of active ingredients combined with the whole plant extract. Our aim was to study the effect of whole ginseng, enriched in the anti-tumoral Rh2 component and other ginsenosides (Ginseng Rh2+), on the metastatic capacity of non-small cell lung cancer (NSCLC).

METHODS

We evaluated the effects of Ginseng Rh2+ on survival, migration and motility, induction of apoptosis, and expression of its apoptosis-related proteins in non-small cell lung cancer (NSCLC) cells in vitro and on primary tumor growth and metastatic capacity in a syngeneic mouse lung cancer model in vivo. The effects of Ginseng Rh2+ on NSCLC cells were studied in vitro using: a colorimetric tetrazolium salt (XTT) assay, annexin V-FITC/PI, western blotting, wound healing motility assay, Transwell migration and cell adhesion assays. In vivo, mice were inoculated with Lewis mouse lung carcinoma cells subcutaneously to evaluate local tumor growth, or intravenously to evaluate the effects of Ginseng Rh2+ on development of experimental metastases. Mice were treated by intraperitoneal administration of Ginseng Rh2+ (0.005-0.5 g kg) on days 6, 10, and 14 after tumor injection.

RESULTS

We found that Ginseng Rh2+ increased the apoptosis of NSCLC cells in vitro, demonstrating dose dependent down-regulation of the Bcl-2 anti-apoptotic gene and concurrent up-regulation of the Bax pro-apoptotic gene. Ginseng Rh2+ inhibited the tumor cells' capacity to attach to the ECM-related matrix and reduced cell migration. In vivo, Ginseng Rh2+ inhibited local tumor growth and reduced the development of experimental lung metastases.

CONCLUSION

Our study suggests that Ginseng Rh2+ may potentially be used as a therapeutic agent for treatment of NSCLC.

摘要

背景与目的

虽然有多项研究探讨了人参作为活性成分(一种或多种源于提取物的人参皂苷)或整株植物提取物的抗肿瘤作用,但缺乏评估人参活性成分与整株植物提取物联合作用的研究。我们的目的是研究富含抗肿瘤 Rh2 成分和其他人参皂苷的整株人参(Ginseng Rh2+)对非小细胞肺癌(NSCLC)转移能力的影响。

方法

我们评估了 Ginseng Rh2+对 NSCLC 细胞体外生存能力、迁移和运动能力、凋亡诱导以及与凋亡相关蛋白表达的影响,以及在同种异体小鼠肺癌模型中体内原发肿瘤生长和转移能力的影响。体外研究 Ginseng Rh2+对 NSCLC 细胞的作用采用比色四唑盐(XTT)检测、 Annexin V-FITC/PI、Western blot、划痕愈合运动检测、Transwell 迁移和细胞黏附检测。体内,通过皮下接种 Lewis 小鼠肺癌细胞评估 Ginseng Rh2+对局部肿瘤生长的影响,或通过静脉注射评估 Ginseng Rh2+对实验性转移发展的影响。在肿瘤注射后第 6、10 和 14 天,通过腹腔内给予 Ginseng Rh2+(0.005-0.5 g/kg)对小鼠进行治疗。

结果

我们发现 Ginseng Rh2+增加了 NSCLC 细胞的凋亡,显示出 Bcl-2 抗凋亡基因的剂量依赖性下调,同时 Bax 促凋亡基因的上调。Ginseng Rh2+抑制肿瘤细胞与细胞外基质相关基质的黏附能力,并降低细胞迁移能力。体内,Ginseng Rh2+抑制局部肿瘤生长并减少实验性肺转移的发展。

结论

我们的研究表明,Ginseng Rh2+可能潜在地用作 NSCLC 的治疗剂。

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