Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/luc Colon Carcinoma Cells and Tumor-Bearing Animal Model

Author:

Lee Shan-Chih1,Shen Chao-Yu2ORCID,Wang Wei-Hsun3,Lee Yen-Po4,Liang Keng-Wei2ORCID,Chou Ying-Hsiang15ORCID,Tyan Yeu-Sheng12,Hwang Jeng-Jong12ORCID

Affiliation:

1. Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, Taiwan

2. Department of Medical Imaging, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

3. Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50044, Taiwan

4. Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Hsinchu City 30010, Taiwan

5. Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

Abstract

Background: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. Methods: CT26/luc murine colon carcinoma cells and a CT26/luc tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. Results: Rh2 caused cell cycle arrest at the G1 phase in CT26/luc cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice’s sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. Conclusions: The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer.

Funder

Chung Shan Medical University Hospital, Taichung, Taiwan

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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