关键词：
curcumin;heat shock protein 70;toll like receptor 4;alarmin;antineoplastic agent;curcumin;heat shock protein 72;TLR4 protein, human;toll like receptor 4;adolescent;antineoplastic activity;apoptosis;Article;cancer inhibition;cell invasion;cell level;cell proliferation;concentration (parameters);controlled study;enzyme linked immunosorbent assay;extracellular space;Hep-G2 cell line;HepG2TT cell line;human;human cell;liver cancer cell line;male;metastasis;priority journal;protein expression;S phase cell cycle checkpoint;signal transduction;simulation;tumor microenvironment;Western blotting;antagonists and inhibitors;cell cycle S phase;drug effect;genetics;liver tumor;metabolism;metastasis;tumor invasion;Alarmins;Antineoplastic Agents;Apoptosis;Cell Proliferation;Curcumin;Hep G2 Cells;HSP72 Heat-Shock Proteins;Humans;Liver Neoplasms;Neoplasm Invasiveness;Neoplasm Metastasis;S Phase;Toll-Like Receptor 4;Tumor Microenvironment
摘要：
Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium. A thermal tolerance HepG2 (HepG2TT) cell model was established to simulate HSP70 accumulation in the microenvironment. A certain concentration of curcumin was co-cultured with HepG2 and HepG2TT cells to observe the changes of HSP70 and TLR4. Our results revealed that heat stress significantly increased the expression of extracellular HSP70 (eHSP70) and TLR4 (P<0.01), but significantly reduced the expression of intracellular HSP70 (P<0.01). Curcumin inhibited proliferation, invasion, and metastasis of HepG2 cells, caused cells to remain in the DNA S phase, promoted apoptosis, and significantly reduced intracellular HSP70, eHSP70 and TLR4 levels of HepG2TT cells. Following the removal of curcumin, eHSP70 increased again. In summary, our results demonstrated that the antitumor effect of curcumin was related to the inhibition HSP70-TLR4 signaling.
