In vitro three-dimensional culture of hepatocellular carcinoma to measure prognosis and responsiveness to chemotherapeutic agents

Hepatocellular carcinoma (HCC) is considered the sixth most common cancer and the third most common cause of cancer-related death worldwide. In addition, HCC is the second most common cancer, second only to lung cancer, in China (1). Over the last 3 decades, incidence rates and mortality rates have gradually increased in the United States (2). Analysis of HCC data from 1990–2014 from the World Health Organization (WHO) and EU indicated that the mortality rates would continue to increase through 2020 in the EU, North America and Latin America. However, in eastern Asia, the rates are predicted to be two to five fold increase compared with those counties (3). Early diagnosis and effective treatment are significant in HCC; however, HCC is typically diagnosed in late stages when surgical resection is not an option. Chemotherapeutic agents, such as sorafenib and doxorubicin, represent a major therapeutic option to alleviate a locally advanced disease and improve survival rates. However, the tumor structure, its invasive nature and metastatic potential and response to HCC chemotherapies are key factors affecting prognosis. During recent decades, two-dimensional culture has been the most common technique used to test the efficacy and safety of drugs before clinical trials, but two-dimensional culture cannot mimic the complex pathophysiological conditions present in HCC. In addition, the lack of specific growth factors and differentiation factors, which are required to mimic the tumor microenvironment in vivo, causes the drugs to fail to achieve satisfactory effects in clinical trials. Three-dimensional cell culture combined with the advantages of animal research and two-dimensional cell culture, which can simulate the tumor microenvironment in vivo (e.g., cell-cell communication and cell-extracellular matrix interaction), reflect the growth characteristics of HCC and the effectiveness of chemotherapy drugs more accurately than two-dimensional cell culture. Currently, three-dimensional cell culture has become a suitable model for researching expression, migration, invasion, and apoptosis and performing drug screening in HCC.