HepG2 Xenograft Model

Discover how Melior’s unique phenotypic screening platforms can uncover the untapped value of your candidate therapeutic

The most common form of liver cancer, hepatocellular carcinoma (HCC), is the sixth most common cancer and the fourth leading cause of cancer-related deaths worldwide.  In North America and Europe, the primary risk factors that drive these statistics as high as they are include are alcohol consumption, non-alcoholic fatty liver disease (NAFLD), and obesity.  HCC is more common in men than women, with a male-to-female ratio of 2:1. Also incidence of liver cancer increases with age, with the highest rates observed in individuals aged 55-64 years.  HCC has a high mortality rate, with a 5-year survival rate of only 18%.  The poor survival rate is attributed to the late diagnosis of the disease, which often occurs after the cancer has metastasized to other organs.  Therefore, for all of these reasons there exists a high unmet medical need to develop better HCC therapeutics.  Melior’s models of HCC are an important tool towards this goal.

Our HepG2 xenograft model, made using the human derived HepG2 cell line, complements our syngeneic liver cancer model which is made using mouse Hepa1-6 cells.  HepG2 is a human liver cancer cell line that was originally isolated from a patient with hepatocellular carcinoma.   The cells exhibit a high rate of proliferation and are easily maintained in culture making it widely used as a model of liver cancer in basic and preclinical research.  The HepG2 cell line harbors a number of genetic and molecular abnormalities commonly found in liver cancer, including mutations in TP53, CTNNB1, and AXIN1 genes. Additionally, the cells express high levels of alpha-fetoprotein (AFP), which is a marker of liver cancer.  The HepG2 cell line exhibits sensitivity to various chemotherapeutic agents, including doxorubicin, cisplatin, and 5-fluorouracil. The cells are also sensitive to various targeted therapies, such as sorafenib, which is a multi-kinase inhibitor used for the treatment of advanced liver cancer.

Chemotherapy validation in human hepatic cancer HepG2 xenograft model. 5 x106 HepG2 were subcutaneously injected into the rear flank of nude mice. Once the tumor size reached ~100mm3, mice were randomized into vehicle control group (treated with normal saline) and cisplatin group (4 mg/kg, i.p twice/week). Data area mean +/-SEM. N=6 for Vehicle, N=5 for paclitaxel. ** p < 0.01, *** p < 0.001, p < 0.0001 by Student’s t-test.

Melior can initiate your HepG2 tumor model study with very short lead times and with bespoke study design to suit your needs. Including time to establish tumor-bearing mice (~2 weeks) and typical treatment times (3-4 weeks) these studies normally run for approximately 5-6 weeks. The HepG2 xenograft mouse model yields highly reproducible tumor growth curves with small error bars capable of detecting small changes in growth rates will relatively small group sizes.

References:

  1. Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1. doi:10.4103/jcar.JCar_9_16
  2. Gerets HH, Tilmant K, Gerin B, et al. Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol. 2012;28(2):69-87. doi:10.1007/s10565-012-9204-2