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Cited by 387Hepatocellular Carcinoma Treatment and PrognosisViral Infectious Diseases and Gene Expression in InsectsCancer and biochemical research

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

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Arzumanian, Viktoriia A., Kiseleva, Olga I., Poverennaya, Ekaterina V.·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms222313135PMC PMC8658661
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Abstract

Liver cancer is the third leading cause of cancer death worldwide. Representing such a dramatic impact on our lives, liver cancer is a significant public health concern. Sustainable and reliable methods for preventing and treating liver cancer require fundamental research on its molecular mechanisms. Cell lines are treated as in vitro equivalents of tumor tissues, making them a must-have for basic research on the nature of cancer. According to recent discoveries, certified cell lines retain most genetic properties of the original tumor and mimic its microenvironment. On the other hand, modern technologies allowing the deepest level of detail in omics landscapes have shown significant differences even between samples of the same cell line due to cross- and mycoplasma infection. This and other observations suggest that, in some cases, cell cultures are not suitable as cancer models, with limited predictive value for the effectiveness of new treatments. HepG2 is a popular hepatic cell line. It is used in a wide range of studies, from the oncogenesis to the cytotoxicity of substances on the liver. In this regard, we set out to collect up-to-date information on the HepG2 cell line to assess whether the level of heterogeneity of the cell line allows in vitro biomedical studies as a model with guaranteed production and quality.

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  • HepG2 is a derivative of hepatoblastoma (HB), confirmed by Wnt/β-catenin signaling abnormalities and genetic features typical of HB, and its tumor origin may skew responses relative to normal hepatocytes.

    “Although HepG2 is commonly classified as hepatocellular carcinoma, modern molecular cytogenetic data classify it as a derivative of hepatoblastoma (HB), which is confirmed by characteristic abnormalities in the Wnt/β-catenin signaling pathway and genetic features typical of HB [78].”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [78]

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Authors
Arzumanian, V. A., Kiseleva, O. I., & Poverennaya, E. V.
Affiliations
Institute of Biomedical Chemistry (RU)
Corresponding author
Arzumanian, Viktoriia A.
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-12-04
Volume
22
Issue
23
Pages
13135
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms222313135
PMC
PMC8658661
OpenAlex
W4200230765
Cited by
387
References
191
Citations by year
2026: 86 · 2025: 119 · 2024: 96 · 2023: 59 · 2022: 26
FWCI
5.90
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Russian Science Foundation (20-14-00328)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords
HepG2 cells, liver cancer, hepatocellular carcinoma, cell line heterogeneity, mycoplasma contamination, cross-contamination, in vitro tumor model, cell line quality control, hepatocarcinogenesis, cytotoxicity assay
MeSH terms
Humans, Liver Neoplasms, Proteins, Hepatocytes, Biomedical Research, Metabolome, Hep G2 Cells

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