Ginsenoside Rh1 inhibits colorectal cancer cell migration and invasion in vitro and tumor growth in vivo

Lyu,Xi; Xu,Xiaodong; Song,Ailin; Guo,Jinyi; Zhang,Yawu; Zhang,Youcheng

doi:10.3892/ol.2019.10742

Ginsenoside Rh1 inhibits colorectal cancer cell migration and invasion in vitro and tumor growth in vivo

Authors:
- Xi Lyu
- Xiaodong Xu
- Ailin Song
- Jinyi Guo
- Yawu Zhang
- Youcheng Zhang
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Affiliations: The Sixth Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China, The Second Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
Published online on: August 14, 2019 https://doi.org/10.3892/ol.2019.10742
Pages: 4160-4166
Copyright: © Lyu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third leading cause of cancer‑associated mortality worldwide. Ginsenoside Rh1 (Rh1) is a traditional medicine monomer with antitumor activity; however, the effects of Rh1 in CRC remain to be determined. In the present study, SW620 cells were treated with different concentrations of Rh1. Cell Counting Kit‑8, wound healing and Transwell assays were performed to measure cell viability and proliferation, migration and invasion, respectively. Subsequently, the mRNA expression levels of matrix metallopeptidase (MMP)1, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were detected by reverse transcription‑quantitative PCR analysis. In addition, the protein expression levels of MMP1, MMP3, TIMP3, and total or phosphorylated (p‑)ERK1/2, P38, JNK were detected by western blotting. Furthermore, tumor growth was examined in a nude mouse xenograft model. The results of the present study indicated that Rh1 was not toxic to CRC cells at various concentrations (0, 50 or 100 µM) and treatment durations (24 or 48 h). However, cell proliferation was suppressed by Rh1 in a dose‑dependent manner. Rh1 (100 µM) significantly inhibited cell migration and invasion in vitro. Additionally, Rh1 suppressed the mRNA and protein expression of MMP1 and MMP3, and promoted TIMP3 expression. Rh1 decreased the ratios of p‑P38/P38, p‑ERK1/2/ERK1‑2 and p‑JNK/JNK in vitro and in vivo, which suggested that Rh1 inactivated the mitogen‑activated protein kinase (MAPK) signaling pathway. Notably, Rh1 markedly decreased tumor volume and weight in vivo. In conclusion, the present study demonstrated that Rh1 inhibited the proliferation, migration and invasion of CRC cells in vitro and tumor growth in vivo. This inhibition was at least partially due to the inhibition of MMP1 and MMP3 expression, the increase in TIMP3 expression level and the MAPK signaling pathway inactivation. Therefore, Rh1 may effectively inhibit the development of CRC as an anticancer drug, and may have a supporting effect during CRC treatment.

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