Berberine and metformin treatments prior to IVF improved the pregnancy outcome by normalizing the clinical, endocrine and metabolic parameters in PCOS women. Berberine has a more pronounced therapeutic effect and achieved more live births with fewer side effects than metformin.
Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF-1a inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer. (Cancer Sci 2013; 104: 1690-1696
Resistance to chemotherapy is a primary problem for the effective treatment of ovarian cancer. Recently, increasing evidence has demonstrated that miRNAs modulate many important molecular pathways involved in chemotherapy. Previous studies demonstrated that miR-199a affected ovarian cancer cell resistance to cisplatin (DDP). However, the role of miR-199a and its target genes in determination of ovarian cancer sensitivity to DDP remains unclear. Quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of miR-199a in ovarian cancer tissues and C13* and OV2008 cell lines. After transfection of miR-199a mimic or inhibitor, flow cytometry was used to detect cell apoptosis exposed to DDP. Enzyme-linked immunosorbent assay and Western blot assay were applied to detect tumor necrosis factor-α levels and protein expression levels of Bax, Fas, Fas-associated death domain, and caspase-8. The results indicated that the expression of miR-199a was downregulated and hypoxia-inducible factor 1α (Hif1α) upregulated in the ovarian tumors compared with those in the corresponding normal tissues. Besides, the expression levels of miR-199a were significantly higher in OV2008 cells compared with those in C13* cells. Moreover, suppression of Hif1α reversed the inhibiting function of miR-199a inhibitor on DDP-induced apoptosis in the OV2008 cells. However, overexpression of both miR-199a and Hif1α reduced DDP-induced apoptosis in C13* cells. In conclusion, miR-199a may change DDP resistance in ovarian cancer by regulating Hif1α.
To investigate the relationship between p38 mitogen-activated protein kinase (p38MAPK) and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry (FCM) and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration (IC(50)) of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RT-PCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was (19.7+/-1.04)% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group (P<0.05). The relative reversal rate of A2780/Taxol cells to paclitaxel was (57.18+/-2.01)%. As compared with the control group and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.
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