Norcantharidin alone or in combination with crizotinib induces autophagic cell death in hepatocellular carcinoma by repressing c-Met-mTOR signaling
Bibliographic record
Abstract
// Chao-Yue Sun 1, * , Ying Zhu 1, * , Xiao-Feng Li 2 , Li-Peng Tang 1 , Zu-Qing Su 1 , Xie-Qi Wang 1 , Cai-Yun Li 1 , Hong-Mei Yang 3 , Guang-Juan Zheng 1 and Bing Feng 1 1 Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China 2 Clinical Medical College of Acupuncture and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China 3 School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China * These authors contributed equally to this work Correspondence to: Guang-Juan Zheng, email: zhengguangjuan@163.com Bing Feng, email: bing19831@163.com Keywords: hepatocellular carcinoma; NCTD; autophagy; c-Met; crizotinib Received: July 22, 2017 Accepted: November 15, 2017 Published: December 04, 2017 ABSTRACT There is an urgent need for effective molecular therapies for hepatocellular carcinoma (HCC), the third-leading cause of cancer-related deaths worldwide. Norcantharidin (NCTD), a demethylated derivative of cantharidin, reportedly exhibits anticancer activity against various types of tumors, including HCC, though the mechanisms involved remain largely unknown. Here, we report that NCTD reduces viability of human MHCC-97H (97H) and HepG2 HCC cells, and induces cell death by triggering high levels of autophagy. Moreover, a significant attenuation of tumor growth was observed after NCTD treatment of HepG2 tumors in vivo , and this effect was enhanced by co-treatment with the c-Met inhibitor crizotinib. Interestingly, western blot analyses showed that the cytotoxic autophagy induced by NCTD correlates with a reduction in the phosphorylation status of both c-Met and m-TOR. These results suggest that cytotoxic autophagy resulting from inhibition of c-Met/mTOR signaling may be achieved in HCC by combined NCTD and crizotinib administration. Further studies to validate the therapeutic potential of this approach are warranted.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.003 | 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".