Introduction: Advanced ovarian cancer is the main cause of ovarian cancer deaths, and it is important to seek safe and effective phytochemicals to suppress cancer or lower the chemotherapy resistance of ovarian cancer.Methods: This study evaluated the effect of Triptolide (TPL) on the proliferation, cycle distribution, apoptosis, and ultra-structure of COC1/DDP cells in vitro, as well as the anti-cancer effect and sensibilisation effect of TPL in vivo.Results: The results indicated that TPL could significantly inhibit the growth of COC1/DDP cells (P<0.05), and 3 ng/ml TPL and 50 ng/ml TPL made COC1/DDP cells present obvious apoptosis characteristics and arrest 35% and 55% of COC/DDP cells in the G0/G1 phase, respectively (P<0.05). The animal experiments also indicated that 0.1mg/kg.d TPL significantly reduced the tumour weight and the spleen cell transformation rate (SI), and it lowered the inflammatory factors IL-2 and TNF-a in rat serum (P<0.05). Moreover, the significant reduction of p-Akt and p-GSK3β made the TPL+DDP possess the highest apoptosis rate [(51.13±3.325)%] in COC1/DDP cells.Conclusions: TPL used in combination with DDP may produce a synergistic anti-cancer effect that warrants further investigation for its potential clinical applications in the treatment of epithelial ovarian cancer.

Departmental sources Background: Ferulic acid is an antioxidant phenolic compound derived from plants, which has effects on cancer cells. This study aimed to investigate the effects of ferulic acid on HeLa and Caski human cervical carcinoma cells and the molecular mechanisms involved. Material/Methods: HeLa and Caski human cervical carcinoma cells were grown in culture and treated with increasing doses of ferulic acid. The MTT assay was used to evaluate cell viability. Flow cytometry was performed with 4',6-diamidino-2-phenylindole (DAPI) and Annexin V staining for cell apoptosis. The expression of myeloid leukemia cell differentiation-1 (Mcl-1) protein and MCL-1 mRNA were determined by Western blot and reverse transcriptionpolymerase chain reaction (RT-PCR). Results: Ferulic acid significantly reduced HeLa and Caski cell viability in the concentration range of 4-20 µM (P<0.05). Ferulic acid treatment promoted DNA condensation and significantly increased apoptosis in Caski cells (P<0.05). Ferulic acid treatment resulted in the activation of pro-caspase-3, pro-caspase-8, pro-caspase-9, and PARP. The MTT assay showed that ferulic acid did not reduce the viability of Caski cells treated with the caspase inhibitor, z-VAD-fmk. Ferulic acid reduced the levels of Bcl-2 and Mcl-1, and increased the levels of Bax and reactive oxygen species (ROS). In Caski cells, Akt and PI3K phosphorylation were reduced by ferulic acid in a concentration-dependent manner. Conclusions: The effects of ferulic acid were dose-dependent and resulted in cell cytotoxicity and apoptosis of HeLa and Caski cells, and the PI3K/Akt signaling pathway was down-regulated in Caski cells.

This study was designed to investigate the antitumor activity of triptolide in ovarian cancer inoculated with SKOV3 and SKOV3/cisplatin (DDP) cells, and to assess the mechanisms. In-vivo and in-vitro experiments were designed to evaluate the effects of triptolide on the tumor growth of SKOV3 and SKOV3/DDP cells. The experiments were divided into four groups: a SKOV3 group, a SKOV3 + TP treatment group, a SKOV3/DDP group and a SKOV3/DDP + TP treatment group. The expression of Sorcin, vascular endothelial growth factor and matrix metalloproteinase-2 were detected by western blotting and immunohistochemistry. Tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. In-vitro experiments showed that compared with SKOV3 control group, the level of colony-stimulating factor 1 and expression of Sorcin in SKOV3/DDP was significantly higher. Interestingly, triptolide treatment could reduce colony-stimulating factor 1 level and expression of Sorcin in both SKOV3 and SKOV3/DDP cell lines. In-vivo experiments showed that tissue necrosis area in SKOV3 + TP and SKOV3/DDP + TP was larger than SKOV3 and SKOV3/DDP group, respectively. Triptolide treatment induced apoptosis in both SKOV3 and SKOV3/DDP cells. Compared with SKOV3 group, the size of tumors was large, and the expression of MMP-2, Sorcin and vascular endothelial growth factor was higher in SKOV3/DDP group. Triptolide treatment reduced the size of tumors, and the expression of MMP-2, Sorcin and vascular endothelial growth factor in SKOV3/DDP as well as in SKOV3 tumors. In conclusion, triptolide has antitumor activity in both SKOV3 and SKOV3/DDP cells likely through inducing apoptosis and regulating MMP-2, Sorcin and vascular endothelial growth factor expression.

Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage.