The HepG2 Xenograft Model for Liver Cancer

Speak To An Expert

The Current HCC Treatment Landscape

Surgical resection and liver transplantation are the primary treatments for early-stage HCC, but many patients who present with advanced disease need systemic therapies. Advances in chemotherapy, targeted therapy, and immunotherapy have improved outcomes, but more effective treatments are urgently needed.

Drug discovery in HCC also faces several challenges, including the tumor’s genetic heterogeneity, the immunosuppressive microenvironment, and the development of drug resistance. These factors complicate the identification and validation of new therapeutic targets and hinder the effectiveness of existing treatments. Additionally, the liver’s unique physiology and its role in drug metabolism make it challenging to develop therapies that are both effective and safe.

Melior’s HepG2 xenograft model addresses these challenges by providing a reliable platform for preclinical testing. It mimics the human liver tumor microenvironment, enabling the evaluation of drug efficacy and toxicity in conditions resembling clinical settings and accelerating the development of effective HCC treatments.​

Advantages of the HepG2 xenograft model

  • Scale your research with highly reproducible tumor growth.
  • Utilize natural liver enzyme activity for realistic drug metabolism.
  • Improve data reliability with consistent tumor model performance.
  • Reduce study time with short lead timelines for tumor establishment in mice.

Track tumor progression without sacrifice using the
HepG2-Luc2 xenograft model

As a derivative of the HepG2 cell line, the HepG2-Luc2 xenograft model retains the same stability, reliability, and decades-long track record but has been engineered to express the luciferase 2 (Luc2) gene. Used often in molecular biology for live tracking, Luc2 is a bioluminescent reporter that allows for noninvasively monitoring cells in real time using IVIS and other bioluminescence imaging techniques.

Using the HepG2-Luc2 xenograft model, monitor tumor growth, metastasis, and response to treatment at multiple time points without sacrificing the animal.

Investigate liver cancer in greater detail with our custom services

Unlock the full potential of your liver cancer research with our HepG2 xenograft model. Our specialized services offer precise insights into tumor biology and therapeutic efficacy.

Contact us for more information on our additional and individualized services, including IVIS imaging, PK studies, and metabolic analyses.

Discuss your project with us
  • We chose Melior Discovery because they were responsive and cost effective.  We are staying with them as a chosen scientific partner because of their thoughtful scientific input to experimental design and attention to detail.  Their expertise and flexibility allowed us to quickly adapt the study design and evaluate additional outcome measures to pursue unexpected activity.

    Sridharan Rajamani, Ph.D., Senior Research Scientist

    Gilead Sciences
  • I have been working with Melior on a number of projects over the course of a few years now.  They have been a great partner throughout this time.  The scientists whom I have worked with have been great problem-solvers and were customer focused.

    Jay Lichter

    Avalon Ventures
  • Melior provided State-of-the-art Preclinical Pharmacology Support for a period of nearly a year where a series of in vivo studies were completed on a weekly basis. The staff was extremely user-friendly and the operational processes were excellent. I can recommend Melior without reservation.

    Richard DiMarchi, PhD

    Cox Professor of Chemistry & Gill Chair in Biomolecular Sciences Indiana University, Department of Chemistry
  • Because Melior could do the orthotopic intracranial implants, we were able to do survival studies with brain tumor-bearing animals that were treated with our therapy, showing a beautiful survival with our agent versus control. Talk about something that gets your investors going! These beautiful survival curves with our agent versus control and visual photos are in all of our investor decks because… it's powerful.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Melior works in many therapeutic areas, like CNS, inflammatory disease, GI, cardiovascular, and oncology. I was very pleased that when it came to doing tumor studies, both subcutaneous and intracranial, they did them well. They reported on the studies on time and did the data analysis really well.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Their areas of expertise are extensive, and they are very experienced, responsive, and flexible in terms of how the study is run. Their pricing is reasonable, making them the best option for a young, not well-funded company like ours.

    Maxine Gowen

    Tamuro Bio
  • Melior’s team was very experienced and knowledgeable. They were always very open to suggestions and questions, spending a lot of time helping us feel comfortable with the study design. I would give them very high marks.

    Maxine Gowen

    Tamuro Bio
  • The most important factors in choosing to work with Melior were the fit between the tests they could run and our needs, as well as their tight budget and proximity. Melior was the best fit for our research goals.

    Ira Spector

    SFA Therapeutics

Chemotherapy validation in human hepatocellular carcinoma HepG2 xenograft model. 5 x106 HepG2 cells were subcutaneously injected into the rear flank of nude mice. Once the tumor size reached ~100mm3, mice were randomized into either the vehicle control group (treated with normal saline) or the paclitaxel group (10 mg/kg, i.p once/week). Data are mean +/-SEM. N=6 for Vehicle, N=5 for paclitaxel. ** p < 0.01, *** p < 0.001, p < 0.0001 by Student’s t-test.

Did you know the HepG2 cell line mimics human liver cancer metabolism?

Our HepG2 xenograft model not only supports reliable tumor growth but also replicates human liver cancer metabolism, providing deeper insights into drug efficacy. This unique capability ensures more accurate preclinical results. With customized study designs and short lead times, accelerate your HCC research effectively.

Want to know more? Speak to an expert

Related Services and Solutions

Implement your patient-derived tumor samples in an in vivo liver tumor models

Forecast the success of your targeted liver cancer treatments effectively with customized patient cell-derived mouse xenografts. Explore patient-specific characteristics and expedite the creation of impactful therapeutics using bespoke in vivo models.

Learn more about patient-derived xenograft models

Researching another cancer type?

We have xenograft models for multiple cancer types, including breast, colorectal, brain, and lung cancer.

Explore cancer xenograft models

Need an immunocompetent in vivo model?

Our Hepa 1-6 syngeneic mouse model offers a realistic environment to test your HCC therapeutics in an immunocompetent organism.

Read more about the Hepa 1-6 syngeneic model

Publications

Arzumanian, V. A., Kiseleva, O. I., & Poverennaya, E. V. (2021). The curious case of the HepG2 cell line: 40 years of expertise. International Journal of Molecular Sciences, 22(23), 13135. doi:10.3390/ijms222313135.

Cheng, A. S., Chan, H. L., Leung, W. K., Wong, N., Johnson, P. J., & Sung, J. J. (2003). Specific COX-2 inhibitor, NS-398, suppresses cellular proliferation and induces apoptosis in human hepatocellular carcinoma cells. Cytotechnology, 23, 113–119. doi:10.1016/S0168-1656(03)00135-7.

Schicht, G., Seidemann, L., Haensel, R., Seehofer, D., & Damm, G. (2022). Critical Investigation of the Usability of Hepatoma Cell Lines HepG2 and Huh7 as Models for the Metabolic Representation of Resectable Hepatocellular Carcinoma. Cancers, 14(17), 4227. https://doi.org/10.3390/cancers14174227.

Shahmoradi, S. S., Salehzadeh, A., Ranji, N., & Habibollahi, H. (2023). Trigger of apoptosis in human liver cancer cell line (HepG2) by titanium dioxide nanoparticles functionalized by glutamine and conjugated with thiosemicarbazone. 3 Biotech, 13(6), 195. https://doi.org/10.1007/s13205-023-03609-9.

Tyakht, A. V., Ilina, E. N., Alexeev, D. G., Ischenko, D. S., Gorbachev, A. Y., Semashko, T. A., Larin, A. K., Selezneva, O. V., Kostryukova, E. S., Karalkin, P. A., Vakhrushev, I. V., Kurbatov, L. K., Archakov, A. I., & Govorun, V. M. (2014). RNA-Seq gene expression profiling of HepG2 cells: the influence of experimental factors and comparison with liver tissue. BMC genomics, 15(1), 1108. https://doi.org/10.1186/1471-2164-15-1108.

Frequently Asked Questions

What are the advantages of using the HepG2 xenograft model for liver cancer research?

The HepG2 xenograft model offers highly reproducible tumor growth, natural liver enzyme activity for realistic drug metabolism, consistent tumor model performance, and short lead timelines for tumor establishment in mice. Being an HCC mouse model, it also represents the majority of liver cancers, as over 75% of liver cancers are HCC.

These advantages help streamline clinical development and improve the accuracy of preclinical drug efficacy predictions.

How does the HepG2 xenograft model mimic human liver cancer metabolism?

The HepG2 xenograft model mimics human liver cancer metabolism by replicating key metabolic pathways and enzyme activities characteristic of HCC. HepG2 cells express liver-specific enzymes and proteins such as cytochrome P450 enzymes, albumin, and alpha-fetoprotein, which are crucial for drug metabolism and liver function. Additionally, HepG2 cells maintain essential liver functions like gluconeogenesis, glycogenolysis, and lipid metabolism. They also exhibit the Warburg effect, where cancer cells prefer glycolysis over oxidative phosphorylation, leading to increased glucose uptake and lactate production, mimicking metabolic shifts observed in HCC.

This capability ensures that the HCC mouse model accurately reflects the metabolic environment of human liver cancer, leading to more accurate preclinical results and better predictions of clinical outcomes.

How does the HepG2-Luc2 xenograft model enhance liver cancer research?

The HepG2-Luc2 xenograft model is a derivative of the HepG2 cell line engineered to express the luciferase 2 (Luc2) gene. This bioluminescent reporter allows for noninvasive real-time monitoring of tumor growth, metastasis, and treatment response using IVIS and other bioluminescence imaging techniques, providing precise and dynamic tumor insights without sacrificing the animal.

Citations

  1. Serraino, D., Fratino, L., Piselli, P. (2023). Epidemiological Aspects of Hepatocellular Carcinoma. In: Ettorre, G.M. (eds) Hepatocellular Carcinoma. Updates in Surgery. Springer, Cham. https://doi.org/10.1007/978-3-031-09371-5_1.
  2. Tolou-Ghamari Zahra. (2024). Review of Hepatocellular Carcinoma and Liver Disease Prevalence, New Emirates Medical Journal; Volume 5, e02506882271605. DOI: 10.2174/0102506882271605231211102803. Available at: https://www.benthamscience.com/article/139873.
  3. Pinto-Marques, H; Cardoso, J; Silva, S; Neto, JL; Gonçalves-Reis, M; Proença, D; Mesquita, M; Manso, A; Carapeta, S; Sobral, M; Figueiredo, A; Rodrigues, C; Milheiro, A; Carvalho, A; Perdigoto, R; Barroso, E; Pereira-Leal, J. (2022). A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation. Annals of Surgery 276(5):p 868-874. DOI: 10.1097/SLA.0000000000005637 Available at: https://pubmed.ncbi.nlm.nih.gov/35916378/.
  4. Aden, D., Fogel, A., Plotkin, S. et al. (1979). Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282, 615–616. https://doi.org/10.1038/282615a0.
  5. Sheng-Long Ye, Tadatoshi Takayama, Jeff Geschwind, Jorge A. Marrero, Jean-Pierre Bronowicki, Current Approaches to the Treatment of Early Hepatocellular Carcinoma, The Oncologist, Volume 15, Issue S4, November 2010, Pages 34–41, https://doi.org/10.1634/theoncologist.2010-S4-34.
  6. Kinsey, E.; Lee, H.M. (2024). Management of Hepatocellular Carcinoma in 2024: The Multidisciplinary Paradigm in an Evolving Treatment Landscape. Cancers, 16, 666. https://doi.org/10.3390/cancers16030666.