Mechanism of TTF1-NP induced implanted hepatoma tumor apoptosis in nude mice by endoplasmic reticulum stress pathway / 药学学报

ABSTRACT

This study was designed to investigate the effect of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle (TTF1-NP) on inducing apoptosis of implanted tumour cells in nude mice and the mechanism of endoplasmic reticulum stress pathway. The implanted hepatoma model was established in nude mice, and used to test the drug TTF1-NP in five groups (vehicle, 5 μmol·kg-1 TTF1-NP, 10 μmol·kg-1 TTF1-NP, 20 μmol·kg-1 TTF1-NP and adriamycin). The nude mice were killed after the treatment to determine the tumor growth inhibition rate (IR). Morphological changes of implanted tumor cells were observed by HE staining; apoptosis of tumor cells was detected by TUNEL; the protein expression of GRP78, p-JNK and caspase 12 were analyzed using immunocytochemistry staining and Western blotting. We tested the effects of TTF1-NP on implanted HepG-2 cell tumor growth in nude mice. TTF1-NP-treated mice showed volume of tumor smaller than that of the vehicle-treated mice. The tumor mass of the TTF1-NP-treated mice were significantly reduced than those of the vehicle-treated mice. In addition, the tumor growth rate of the TTF1-NP-treated mice was significantly lower than that of the vehicle-treated mice, and the tumor growth inhibition ratio of the TTF1-NP-treated mice was significantly higher than that of the vehicle-treated mice. TTF1-NP exhibited an inhibitory effect on implanted tumor cells in the model. The IR was 51.2%, 54.2%, 61.8% and 65.9%, respectively. In comparison with the vehicle group, the treated groups exhibited alteration in cell morphology and apoptosis of tumor cells, and expression of GRP78, p-JNK and caspase 12, which were observed by immunocytochemistry staining and Western blotting. Taken together, our results suggest that TTF1-NP induces apoptosis of implanted tumor cells in nude mice and the main mechanism is related to activation of endoplasmic reticulum stress.