Many physiological activities such as cell survival, proliferation, defense, adaptation, and metabolism need to consume energy.
Hepatoma cells can quickly start stress responses like multidrug resistance (MDR) requiring
adenosine triphosphate (
ATP) consumption after administration of chemotherapeutics. We employed
CCK-8 assay to evaluate cell viability and the flow cytometry to confirm apoptosis and
necrosis. ELISA kit was used to determine intracellular levels of
ATP in lysates. Western blot was employed to analyze the expressions of key
enzymes involved in energy metabolism. We found that
doxorubicin (DOX) potently stimulated apoptosis at a low dose and even induced
necrosis at a high dose in SMMC-7721. DHZCP combined with DOX at low or middle dose enhanced the synergistic antihepatoma effect. Results indicated that
Dahuang Zhechong Pill (DHZCP) inhibited the expressions of several key
enzymes involved in oxidative phosphorylation and reduced intracellular
ATP levels. The combination of DHZCP with DOX reversed the elevation of intracellular
ATP levels, and a significantly synergistic antitumor effect was observed. DHZCP could not only strengthen the
therapeutic effects of chemotherapeutic drugs but also decrease the doses of chemotherapeutic drugs and the incidences of adverse reactions, providing novel strategies for clinical treatment of
liver cancer.