Sesquiterpene lactone 6‑O‑angeloylplenolin reverses vincristine resistance by inhibiting YB‑1 nuclear translocation in colon carcinoma cells
- Changlong Li
- Hezhen Wu
- Yanfang Yang
- Jianwen Liu
- Zhenwen Chen
Affiliations: School of Basic Medical Science, Capital Medical University, Beijing 100069, P.R. China, Key Laboratory of Resources and Chemistry of Chinese Medicine of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan, Hubei 430061, P.R. China, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P.R. China
- Published online on: April 27, 2018 https://doi.org/10.3892/ol.2018.8592
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Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6‑O‑angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 (MDR1) and increasing the intracellular concentration of anticancer drugs. A reduction in P‑glycoprotein expression (encoded by MDR1) was observed in parallel with a decline in mRNA expression in vincristine‑resistant HCT (HCT‑8/VCR) cells treated with 6‑O‑angeloylplenolin. In addition, 6‑O‑angeloylplenolin suppressed the activity of the MDR1 gene promoter. Treatment with 6‑O‑angeloylplenolin also decreased the amount of the specific protein complex that interacted with the MDR1 gene promoter in HCT‑8/VCR cells, potentially leading to the suppression of MDR1 expression. Treatment with 6‑O‑angeloylplenolin inhibited the nuclear translocation of Y‑box binding protein‑1 in HCT‑8/VCR cells treated with 6‑O‑angeloylplenolin, contributing to the negative regulation of MDR1. Finally, 6‑O‑angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6‑O‑angeloylplenolin exhibited a MDR‑reversing effect by downregulating MDR1 expression and could represent a novel adjuvant agent for chemotherapy.