The Role of Huh7 and HepG2 Cell Lines in Advancing Liver Cancer Research

The discovery of Huh7 and HepG2 cells has significantly transformed liver cancer research, providing oncologists with a better understanding of the disease’s behavior.  

Both Huh7 and HepG2 are immortalized human liver cancer cell lines obtained from hepatomas. Besides their widespread usage in pharmacological research, the cell lines may also serve as models for normal organ functioning.  

A sample of Huh7 cells can offer useful clues into a liver’s overall health and drug metabolism.  

But despite their general similarities, Huh7 and HepG2 serve distinct roles.  

Huh7 cells mostly help in the study of the hepatitis C virus (HCV). Researchers can study Huh7 models to learn more about the virus’s behavior, including its ideal breeding environment and conditions for replication.  

Huh7 cells are also critical in the study of liver cancer. That’s due to their ability to support the HCV virus.  

Meanwhile, HepG2 is commonly used in the study of liver metabolism, drug interactions, and non-cancerous diseases.  

What Are Huh7 Cells? 

Huh7 is a popular human liver cancer cell. It’s one of the continuous immortalized cell lines obtained from a 57-year-old Japanese male’s carcinogenic liver tumor in 1982.  

Huh7 cells are well-differentiated. The cells have demonstrated promise in supporting liver cancer research, enabling researchers to investigate the disease in vitro.  

The Huh7 cells are especially noted for their ability to support hepatitis C virus replication. Due to those properties, researchers may also rely on the cells to study HCV.  

As the liver is largely responsible for drug metabolism, analyzing Huh7 cell lines can help with new drug testing too.  

Huh7 Cell Line Characteristics 

The Huh7 cell line exhibits similar biological properties to primary hepatocytes (main liver cells), including the ability to break down certain metabolites. The cells are also capable of proliferating in 2D monolayers.  

And like most mammalian cells, Huh7 can be cultured in certain media.  

For optimal growth, preserve the cells in Dulbecco’s Modified Eagle Medium (DMEM) basal medium supplemented with fetal bovine serum (FBS).  

What Are HepG2 Cells? 

HepG2 is another common liver cancer cell line widely used in advancing carcinogenic research. It derives from a hepatocellular carcinoma, pretty much like Huh7.  

When you compare Huh7 vs. HepG2 cell line, HepG2 stands out for its efficacy in aiding liver toxicology tests and drug metabolism. The cell also supports liver cancer research due to its high proliferation rate.  

HepG2 was originally obtained from the carcinogenic liver tissues of a 15-year-old Caucasian male.  

HepG2 Unique Characteristics 

The HepG2 cell line has a unique ability to secrete plasma proteins, including transferrin, albumin, and plasminogen. It also proliferates remarkably fast, making it even easier to culture in research laboratories.  

A single HepG2 cell can replicate indefinitely in monolayers, providing multiple samples for control experiments.  

The HepG2 cell line is biologically similar to primary hepatocytes as far as drug metabolism and transportation.  

However, the cells exhibit altered expression of certain liver functions – such as cytochrome P450 enzymes – compared to healthy hepatic cells. 

The Role of Huh7 and HepG2 in Advancing Liver Cancer Research

1. Studying HCC’s Biological Mechanisms

Huh7 and HepG2 have both demonstrated promise in studying the biological mechanisms of hepatocellular carcinoma cells (HCCs).  

HCCs are carcinogenic cells that derive from primary hepatocytes. They represent the most common type of hepatic cancer and are often diagnosed in individuals with chronic liver cirrhosis.  

By analyzing Huh7 and HepG2 cell lines, researchers can effectively understand HCCs’ genetic composition and molecular structures. Findings from these diagnostic procedures are then used to formulate early interventions, such as producing custom antibodies.  

One of Huh7’s noteworthy use cases is analyzing the biological effects of various oncological markers. Those include Matrix Metalloproteinase 9 (MMP9) and Ak protein kinase (AKT).  

Meanwhile, HepG2 may help analyze the p53 tumor suppressor pathway.

2. Modeling Viral-induced Hepatic Cancers

Hepatitis C virus is a leading cause of hepatic cancer.  

HCV initially triggers chronic liver inflammation. If untreated, the swelling gradually develops into cirrhosis and, eventually, liver cancer.  

Huh7 cell applications in HCV research are well-documented.  

The cell line is highly permissive for the HCV virus. Therefore, it can serve as a model for investigating HCV-induced hepatic cancer.  

Huh7 may also be instrumental in developing HCV treatments, preventing the disease from degenerating into full-blown liver cancer. 

3. Creating Xenographs

Xenographs are cells, tissues, or organs transplanted to a recipient of a different species from the donor.  

As Huh7 and HepG2 derive from hepatomas, researchers can inject these cells into nonhuman tissue models to better analyze tumor growth.  

The new cell line-derived xenographs offer key insights into the angiogenesis, proliferation, and metastasis of carcinogenic cells. It enables researchers to identify biomarkers in a more controlled and predictable environment.  

A robust Huh7 cell culture protocol is necessary while creating xenographs. The cultures must be handled hygienically to avoid contamination, which could reduce the research’s outcome.  

Besides, laboratories must embrace advanced culture management techniques like cryoprotective cell preservation.  

In cryoprotective cell preservation, technicians utilize cryoprotective agents (CPAs) to preserve cultures under frigid conditions of -320.8° Fahrenheit (- 196° Celsius). It temporarily denatures cellular functions without damaging the cultured cells.  

Cryoprotective preservation particularly minimizes damage caused by ice crystal formation. 

4. Analyzing Metastatic Potential

Hepatic cancer cells begin small. If undetected long enough, the cells can proliferate and metastasize to other organs and tissues.  

Huh7 cells metastasize moderately, while HepG2 cells typically lack metastatic potential. Researchers can compare both cells with more aggressive cell lines like Mahlavu and SNU423 to better understand HCC’s metastatic potential.  

Insights from such analyses may support antibody production, too. By knowing how fast HCC spreads, researchers are able to pinpoint the antibodies most responsible for inhibiting the disease’s progression.  

Increasing Huh7 cell transfection efficiency is critical when using this cell line to study metastatic potential.  

A higher transfection efficacy implies the cell is more receptive to foreign genetic material. As such, it’s easily impacted by metastasizing cancerous cells.

5. Investigating Apoptosis and Autophagy

Apoptosis refers to programmed cell death, while autophagy is cellular recycling.  

Both mechanisms are critical in analyzing the biological mechanisms of liver cancer cells.  

According to a study, inhibiting autophagy can slow down the growth and eventually induce apoptosis of cancer cells.  

Autophagy notably suppresses the proliferation of HepG2 cells. This enables researchers to track the efficacy of the prescribed HCC treatments.  

6. Simulating Healthy Liver Functioning

Huh7 and HepG2 may also help to analyze normal liver functioning, including metabolism.  

Multiple findings indicate that metabolic dysregulation increases liver cancer risks. Therefore, scoping for early warning signs of metabolic disorders can help with early HCC detection.  

Both Huh7 and HepG2 exhibit many characteristics of primary hepatocytes.  

HepG2 notably retains the ability to synthesize urea and produce albumin. It can also regulate cytochrome P450 (CYP) enzyme activity, albeit less effectively than healthy hepatocytes.  

Anomalous patterns in Huh7 and HepG2 cellular mechanisms may point to metabolic dysregulation. Researchers can then recommend proper interventions before the condition escalates to full-blown HCC. 

7. Evaluating Drug Efficacy

The efficiency of drug metabolism impacts the body’s ability to successfully fend off infections.  

If the liver takes abnormally long to metabolize chemotherapy medications, an initially unproblematic tumor can proliferate aggressively and spiral out of control.  

Huh7 and drug metabolism studies point to the cell line’s ability to support the analysis of hepatic drug interactions.  

Both Huh7 and HepG2 provide a low-cost way to screen anti-carcinogenic compounds. Besides, researchers can use the cell lines to assess the efficacy of a current thermotherapy plan.  

Huh7 and HepG2 may also prove useful in gauging the effectiveness of combination therapies. That’s significant, considering that a multi-pronged pharmaceutical approach is often critical when dealing with aggressive HCC.

8. Assessing Drug Resistance and Toxicity

Drug resistance isn’t only a major impediment to HCC treatment. Subjecting a cancer patient to ineffective medications can also ruin their already compromised immune systems.  

Fortunately, Huh7 and HepG2 cells may provide useful insights into acquired drug resistance.  

Researchers have since developed Huh7 cells to be resistant to first-line HCC medications like sorafenib. By understanding what doesn’t work, oncologists are able to adjust their chemotherapy plans accordingly.  

Huh7 and HepG2 cells may help in predicting drug-induced hepatotoxicity.  

The cell lines enable oncologists to assess the potential impact of new therapies long before administering them.

9. Developing Advanced 3D Cell Cultures

As Huh7 and HepG2 cells resemble primary hepatocytes, they’re easy to grow in 3D spheroids. 3D spheroids utilize a three-dimensional culture medium that simulates the complex physiological environment of an actual tumor.  

This produces better outcomes than the conventional two-dimensional (2D) cultures, which require developing cells in flat layers.  

Subjecting Huh2 and HepG2 cells to 3D spheroids enables a more accurate analysis of tumor behavior, including growth, proliferation, and differentiation. It also helps researchers to better understand drug interactions. 

10. Exploring Signaling Pathways

Both Huh7 and HepG2 cell lines may help investigate various HCC signaling routes. Commonly targeted pathways include the Wnt/β-catenin and PI3K/Akt.  

First, oncologists carefully analyze these signaling cascades in vivo. The pathways are then manipulated in cell cultures with a view to identifying newer therapeutic targets.  

Pathway manipulation follows a similar concept to gene synthesis, in that it both seeks to boost a subject’s immunity by leveraging novel methodologies.   

However, gene synthesis involves producing entirely new genetic materials rather than discovering previously hidden mechanisms.  

Wrap Up 

Huh7 and HepG2 advance liver cancer research by serving as reliable in vitro models for studying the disease’s behavior. Both cell lines have proven effective at investigating carcinogenic activities that are challenging to study in live patients.  

However, the two cell lines are functionally distinct. Keep that in mind while searching for a Huh7 cell line supplier. As previously stated, Huh7 cells are most effective at studying the hepatitis C virus. HepG2 cell lines are generally useful in investigating liver metabolism and drug interactions.