Bufalin inhibits gastric cancer invasion and metastasis by down-regulating Wnt/ASCL2 expression
Bibliographic record
Abstract
// Jie Wang 1, * , Han Cai 1, * , Yue Xia 1, * , Shiying Wang 2 , Likai Xing 1 , Chao Chen 1 , Yong Zhang 1 , Jie Xu 1 , Peihao Yin 1 , Yiming Jiang 1 , Ronghua Zhao 3 , Qingshong Zuo 1 and Teng Chen 1, 4 1 Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China 2 Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China 3 Department of Medical, Virogin Biotech Ltd., Vancouver, British Columbia V6S 2L9, Canada 4 Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Shanghai 200062, China * These authors have contributed equally to this work Correspondence to: Teng Chen, email: 13801842406@163.com Qingshong Zuo, email: zqsadsl123@sina.com Keywords: bufalin; gastric cancer; invasion and metastasis; Wnt/ASCL2 signaling; EMT Received: September 28, 2017 Accepted: January 02, 2018 Epub: January 11, 2018 Published: May 04, 2018 ABSTRACT Achaete-scute-like 2 (ASCL2) is a transcription factor containing a basic helix-loop-helix (bHLH) domain and is a downstream target of Wnt signaling in intestinal stem cells. Bufalin is the primary active ingredient in Chan Su, a traditional Chinese medicine obtained from the skin and parotid venom glands of toads. The purpose of this study was to research the anti-invasion and anti-metastasis activity of bufalin in gastric cancer and to identify the potential mechanism. Bufalin inhibited gastric cancer cell invasion and metastasis, suppressed cancer cell colony formation, and inhibited the growth of subcutaneous xenografted tumors in nude mice. Furthermore, bufalin inhibited ASCL2 expression and down-regulated the expression of invasion-related genes such as MMP2, MMP9, and vimentin, thereby suppressing epithelial-mesenchymal transition (EMT) in gastric cancer. A Wnt signaling inhibitor (XAV939) down-regulated invasion and the expression of ASCL2, β-catenin, and vimentin but up-regulated E-cadherin expression. In nude mice, bufalin inhibited the tumorigenic behavior of gastric cancer cells, induced cancer cell apoptosis, and regulated invasion-related gene expression. Together, our results suggest that bufalin arrests invasion and metastasis and that its mechanism of action may involve down-regulating Wnt/ASCL2 expression.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".