Evidence map›Paper›PMID 38954975›Full record

ArticleTranslational oncology2024

CuET overcomes regorafenib resistance by inhibiting epithelial-mesenchymal transition through suppression of the ERK pathway in hepatocellular carcinoma.

Ding Ma, Shuwen Liu, Kua Liu, Qinyu He, Lili Hu, Weiwei Shi, Yin Cao, Guang Zhang, Qilei Xin, Zhongxia Wang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Synergistic mechanisms and clinical translation of regorafenib combination therapies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ding MaJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China; Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shuwen LiuJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Kua LiuJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Qinyu HeJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Lili HuDepartment of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Weiwei ShiJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Yin CaoJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Guang ZhangJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Qilei XinJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China.
Zhongxia WangJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China. Electronic address: freud_t@126.com.
Junhua WuJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China. Electronic address: wujunhua@nju.edu.cn.
Chunping JiangJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong 250117, China; State Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093 China; Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China. Electronic address: chunpingjiang@nju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeRegorafenib was approved by the US Food and Drug Administration (FDA) for hepatocellular carcinoma (HCC) patients showing progress on sorafenib treatment. However, there is an inevitably high rate of drug resistance associated with regorafenib, which reduces its effectiveness in clinical treatment. Thus, there is an urgent need to find a potential way to solve the problem of regorafenib resistance. The metabolite of disulfiram complexed with copper, the Diethyldithiocarbamate-copper complex (CuET), has been found to be an effective anticancer drug candidate. In the present study, we aimed to evaluate the effect of CuET on regorafenib resistance in HCC and uncover the associated mechanism. EXPERIMENTAL APPROACH: Regorafenib-resistant HCC strains were constructed by applying an increasing concentration gradient. This study employed a comprehensive range of methodologies, including the cell counting kit-8 (CCK-8) assay, colony formation assay, cell cycle analysis, wound healing assay, Transwell assay, tumor xenograft model, and immunohistochemical analysis. These methods were utilized to investigate the antitumor activity of CuET, assess the combined effect of regorafenib and CuET, and elucidate the molecular mechanism underlying CuET-mediated regorafenib resistance. KEY

resultsThe inhibitory effect of regorafenib on cell survival, proliferation and migration was decreased in regorafenib-resistant MHCC-97H (MHCC-97H/REGO) cells compared with parental cells. CuET demonstrated significant inhibitory effects on cell survival, proliferation, and migration of various HCC cell lines. CuET restored the sensitivity of MHCC-97H/REGO HCC cells to regorafenib in vitro and in vivo. Mechanistically, CuET reverses regorafenib resistance in HCC by suppressing epithelial-mesenchymal transition (EMT) through inhibition of the ERK signaling pathway. CONCLUSION AND IMPLICATIONS: Taken together, the results of this study demonstrated that CuET inhibited the activation of the ERK signaling pathway, leading to the suppression of the epithelial-mesenchymal transition (EMT) and subsequently reversing regorafenib resistance in HCC both in vivo and in vitro. This study provides a new idea and potential strategy to improve the treatment of regorafenib-resistant HCC.

Indexed as

CuETHCCRegorafenibRegorafenib-resistant MHCC-97HReversal of regorafenib resistance

Identifiers

PMID38954975
PMCPMC11267041

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.