Reversal effect of ginsenoside Rh2 on oxaliplatin‑resistant colon cancer cells and its mechanism

Ma,Jun; Gao,Guangyi; Lu,Hong; Fang,Dong; Li,Lingchang; Wei,Guoli; Chen,Aifei; Yang,Yong; Zhang,Hongying; Huo,Jiege

doi:10.3892/etm.2019.7604

Reversal effect of ginsenoside Rh2 on oxaliplatin‑resistant colon cancer cells and its mechanism

Authors:
- Jun Ma
- Guangyi Gao
- Hong Lu
- Dong Fang
- Lingchang Li
- Guoli Wei
- Aifei Chen
- Yong Yang
- Hongying Zhang
- Jiege Huo
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Affiliations: Department of Oncology, Huai'an TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Huai'an, Jiangsu 223001, P.R. China, Department of Traditional Chinese Medicine, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223001, P.R. China, Department of Oncology, Changshu No. 1 People's Hospital, Changshu, Jiangsu 215500, P.R. China, Department of Oncology, Zhenjiang Hospital of Integrated Traditional and Western Medicine, Zhenjiang, Jiangsu 212000, P.R. China, Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China, Department of Oncology, Huai'an Hospital of Chinese Medicine, Huai'an, Jiangsu 223001, P.R. China
Published online on: May 23, 2019 https://doi.org/10.3892/etm.2019.7604
Pages: 630-636
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemotherapy is an important treatment modality for colon cancer, however, drug resistance is the main factor leading to treatment failure. Ginsenoside Rh2 (G‑Rh2), the main bioactive metabolite of ginseng, is known to possess the ability to potently induce cell apoptosis, inhibit cell proliferation and reverse multidrug resistance in a variety of cancer cells. The present study examined the effect of G‑Rh2 on oxaliplatin (L‑OHP)‑resistant colon cancer cells and its potential mechanism. L‑OHP‑resistant colon cancer cells (LoVo/L‑OHP) and LoVo cells were used in the present study. The effect of G‑Rh2 on LoVo/L‑OHP and LoVo cell proliferation was measured using a 3‑(4,5 dimethylthiazol‑z‑yl)‑3,5‑diphenyltetrazolium bromide assay. The effects of G‑Rh2 on LoVo/L‑OHP and LoVo cell apoptosis were detected by flow cytometry. The mRNA and protein expression of apoptosis‑related genes Bax, Bcl‑2 and caspase‑3, drug resistance‑related genes P‑glycoprotein (P‑gp) and Smad4, were determined in LoVo/L‑OHP and LoVo cells treated with G‑Rh2 by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. G‑Rh2 treatment significantly inhibited the proliferation and induced the apoptosis of LoVo/L‑OHP and LoVo cells. In addition, G‑Rh2 treatment resulted in a significant increase in pro‑apoptotic factors, Bax and caspase‑3, and decrease in anti‑apoptotic factor Bcl‑2 in the LoVo/L‑OHP and LoVo cells. Furthermore, G‑Rh2 treatment significantly decreased the levels of P‑gp and increased the levels of Smad4 in the LoVo/L‑OHP and LoVo cells. It was found that L‑OHP had no significant effects on LoVo/L‑OHP cell proliferation or apoptosis, whereas G‑Rh2 + L‑OHP treatment significantly inhibited LoVo/L‑OHP cell proliferation and induced apoptosis. L‑OHP had no significant effects on the expression of P‑gp, Smad4, Bcl‑2, Bax or caspase‑3 in LoVo/L‑OHP cells. Treatment with G‑Rh2 + L‑OHP significantly reduced the expression of P‑gp and Bcl‑2, and enhanced the expression levels of Smad4, Bax and caspase‑3. These findings demonstrated that G‑Rh2 reversed the drug resistance of LoVo/L‑OHP cells to L‑OHP, and this may be mediated by inhibiting cell proliferation and promoting apoptosis and regulating the expression of drug resistance genes. These results suggest that G‑Rh2 may function as a potent anticancer drug for drug resistance in colon cancer treatment.

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