Yue-Jun Li1,2, Lin-Li Liao3, Pei Liu3, Ping Tang1,2, Hong Wang1,2, Qing-Hua Peng4. 1. Department of Oncology, the Third Affiliated Hospital of Hunan University of Chinese Medicine, Zhuzhou, 412000, Hunan Province, China. 2. Department of Oncology, the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine, Zhuzhou, 412000, Hunan Province, China. 3. Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China. 4. Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China. pqh410007@126.com.
Abstract
OBJECTIVE: To investigate a previously uncharacterized function of Sijunzi Decoction (SJZD) in inhibition of gastric cancer stem cells (GCSCs). METHODS: MKN74 and MKN45, two CD44 positive gastric cancer cell lines with stem cell properties were used. The cells were divided into 2 groups. Treatment group was treated with SJZD (1-5 mg/mL) for indicated time (48 h-14 days). The control group was treated with equal volume of phosphate buffered saline. Cell Counting Assay Kit-8 were used to measure cell viability. Spheroid colony formation and GCSCs marker expression were performed to determine GCSCs stemness. Cell fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of β-catenin after SJZD treatment, respectively. RESULTS: SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines (P<0.05). Moreover, SJZD dramatically inhibited formation of spheroid colony and expression of GCSC markers in GC cells (P<0.05). Mechanistically, SJZD reduced nuclear accumulation and DNA binding activity of β-catenin (P<0.05), the key regulator for maintaining CSC stemness. CONCLUSION: SJZD inhibits GCSCs by attenuating the transcriptional activity of β-catenin.
OBJECTIVE: To investigate a previously uncharacterized function of Sijunzi Decoction (SJZD) in inhibition of gastric cancer stem cells (GCSCs). METHODS: MKN74 and MKN45, two CD44 positive gastric cancer cell lines with stem cell properties were used. The cells were divided into 2 groups. Treatment group was treated with SJZD (1-5 mg/mL) for indicated time (48 h-14 days). The control group was treated with equal volume of phosphate buffered saline. Cell Counting Assay Kit-8 were used to measure cell viability. Spheroid colony formation and GCSCs marker expression were performed to determine GCSCs stemness. Cell fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of β-catenin after SJZD treatment, respectively. RESULTS: SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines (P<0.05). Moreover, SJZD dramatically inhibited formation of spheroid colony and expression of GCSC markers in GC cells (P<0.05). Mechanistically, SJZD reduced nuclear accumulation and DNA binding activity of β-catenin (P<0.05), the key regulator for maintaining CSC stemness. CONCLUSION: SJZD inhibits GCSCs by attenuating the transcriptional activity of β-catenin.
Authors: Michael F Clarke; John E Dick; Peter B Dirks; Connie J Eaves; Catriona H M Jamieson; D Leanne Jones; Jane Visvader; Irving L Weissman; Geoffrey M Wahl Journal: Cancer Res Date: 2006-09-21 Impact factor: 12.701
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