Hepatocellular Carcinoma and Chemotherapy: The Role of p53

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver. A major proportion of HCCs also present mutation of the gene that encodes p53, which confers chemoresistance. The main goal of this work is to investigate the effect of cisplatin, doxorubicin and 5-fluoruracil (5-FU) in three human HCC cell lines which differ in p53 expression. Methods: HepG2 (expressing normal p53), HuH7 (expressing mutated p53) and Hep3B2.1-7 (not expressing p53) cell lines were cultivated in the presence of cisplatin, doxorubicin and 5-FU. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay). The type of cell death and Bax and Bcl2 activation were assessed by flow cytometry. Results: It was found that for all of the cell lines studied, the agent that gave the most satisfactory results was doxorubicin. 5-FU demonstrated no activity in these cell lines. Conclusions: For all the cell lines studied, doxorubicin was the most satisfactory agent. In HepG2 and HuH7 cell lines, it can activate Bax with statistical significance.

Silencing of solute carrier family 13 member 5 disrupts energy homeostasis and inhibits proliferation of human hepatocarcinoma cells

“…It is well-known that the transcription of the p21 gene is positively regulated by wild-type p53 protein (35). Given that HepG2 (wild-type p53) and Huh7 (mutant p53) cells hold different statuses of the p53 gene, the p53 mutation in Huh7 cells may contribute to the low level of p21 expression (36). Although deciphering the exact effects of p53 on the expression of p21 is out of the scope of this study, it is clear that induction of p21 by SLC13A5 silencing may contribute to the observed cell cycle arrest in HepG2 but not in Huh7 cells.…”

Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular Carcinoma

“…HCC develops in a complex and progressive process, due to several genetic and epigenetic modifications, in a rich oxidative stress environment [15,16]. These modifications induce autonomous cellular growth and consequent cell cycle deregulation, as well as several mutations in key proteins, such as P53, P21 and β-catenin [14,[16][17][18].…”

“…Palliative therapies include chemotherapy and radiotherapy. However, due to the chemoresistant and radioresistant HCC profile, these therapies often fail and are only applied in order to improve the patient's quality of life [18].…”

Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma: Correlation with Glucose Transporters and p53 Expression

“…[1][2][3][4] This happens because there are differences in the response to these therapies due, at least in part, to the heterogeneity in expression of genes linked to chemoresistance and radioresistance, where the tumor suppressor gene p53 has a very important role. 5,6 Thus, it is important to find diagnostic tools to identify these genetic differences in order to develop more personalized therapies and increase the therapeutic success.…”