Fig
Fig. respective control (C). 12885_2020_7164_MOESM1_ESM.pptx (145K) GUID:?3BC5E891-897B-4972-9D96-AD657FD28030 Additional file 2: Suppl. Fig. 2. Statins and zoledronic acid (ZOL) do not modulate the expression of but downregulate in A2780 cells. A2780 cells were treated with increasing concentrations of atorvastatin (ATO), simvastatin (SIM), rosuvastatin (ROSU) or ZOL for 24 h. Expression of and was assessed by real-time-PCR. Data are shown as mean SEM of at least three individual experiments. *< 0.05; **< 0.01; ***< 0.001 vs. respective control (0 M). Flunixin meglumine 12885_2020_7164_MOESM2_ESM.pptx (179K) GUID:?1E86B074-C879-4026-B757-D9A36A410BF7 Additional file 3: Suppl. Fig. 3. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) specifically rescue farnesylation or geranylgeranylation and vitality upon mevalonate pathway inhibition in IGROV1 and A2780 cells. a. Flunixin meglumine IGROV1 cells were treated with simvastatin (SIM; 10 M) or zoledronic acid (ZOL; 50 M), and supplemented with either FPP (50 M) or GGPP (50 M). Farnesylation of Ras, geranylgeranylation of Rap1A and cleavage of poly (ADP-ribose) polymerase (cPARP) were assessed by western blotting. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as loading control. The figures show representative blots which were cropped from initial images. Full-length blots are offered in Suppl. Fig. 7. Images were detected using GelCapture 7.0.18 software. b. A2780 cells were treated with atorvastatin (ATO), SIM, rosuvastatin (ROSU) or ZOL and supplemented with 10 M of either FPP or GGPP for 48 h. Cell vitality was assessed by CellTiterBlue? assay. Data are shown as mean SEM of at least three individual experiments. *< 0.05; **< 0.01; ***< 0.001 vs. Flunixin meglumine respective control (C). #< 0.05; ##< 0.01; ###< 0.001 vs. respective treatment (-). 12885_2020_7164_MOESM3_ESM.pptx (164K) GUID:?AA544076-5A92-41D4-BD55-D3AAD316EBAA Additional file 4: Suppl. Fig. 4. A2780CIS are relative resistant to cisplatin and undergo apoptosis upon mevalonate pathway inhibition with simvastatin (SIM). a. A2780 and A2780CIs usually cells were treated with increasing concentrations of cisplatin. Cell vitality was assessed by CellTiterBlue? assay (left axis), whereas apoptosis was assessed by Caspase 3/7 Glo? assay (right axis). Data are shown as mean standard deviation of at least three individual experiments. b. A2780CIs usually cells were treated with increasing concentrations of SIM for 48 h. Farnesylation of Ras, geranylgeranylation of Rap1a, and cleavage of poly (ADP-ribose) polymerase (cPARP) were assessed by western blotting. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as loading control. The figures show representative blots Flunixin meglumine which were cropped from initial images. Full-length blots are offered in Suppl. Fig. 8. Images were detected using GelCapture 7.0.18 software. Expression of was assessed by real-time-PCR. Data are shown as mean SEM of at least three individual experiments. **< 0.01; ***< 0.001 vs. respective control (0 M). 12885_2020_7164_MOESM4_ESM.pptx (317K) GUID:?2DF7A570-8FE3-4F02-82C8-4F756A19B138 Additional file 5: Suppl. Fig. 5. Uncropped Western Blots for Fig. ?Fig.1a.1a. The physique shows all initial uncropped blots. As some membranes were used to simultaneously detect Ras and cleaved PARP (after trimming), the pictures here also include the FGF1 cleaved PARP initial blots utilized for Fig. ?Fig.2a2a to keep the originality. All initial blots for GAPDH are also included. Representative cropped GAPDH images are shown in Fig. ?Fig.11a. 12885_2020_7164_MOESM5_ESM.pptx Flunixin meglumine (2.7M) GUID:?3B6FB5C0-87BC-4C7B-9804-73DB3E49F518 Additional file 6: Suppl. Fig. 6. Uncropped Western Blots for Fig. ?Fig.2a.2a. The physique shows all initial uncropped blots. As some membranes were used to simultaneously detect Ras and cleaved PARP (after trimming), the pictures here also include the Ras initial blots utilized for Fig. ?Fig.1a1a to keep the originality. All initial blots for GAPDH are also included. Representative cropped GAPDH images are shown in Fig. ?Fig.22a. 12885_2020_7164_MOESM6_ESM.pptx (1.8M) GUID:?BD013DFF-C1B6-42B8-8AEC-762FC72E1E6B Additional file 7: Suppl. Fig. 7. Uncropped Western Blots for Supplementary Physique 3a. 12885_2020_7164_MOESM7_ESM.pptx (453K) GUID:?3D2751EA-AD20-4813-A898-6DB1820F2047 Additional file 8: Suppl. Fig. 8. Uncropped Western Blots for Supplementary Physique 4b. 12885_2020_7164_MOESM8_ESM.pptx (605K) GUID:?E200CB0F-9A37-41B3-96AE-64B65F1080F5 Data Availability StatementThe datasets used and/or analyzed during the current study are available from your corresponding author on reasonable request. Abstract Background Ovarian cancer remains the most fatal gynecological malignancy. Current therapeutic options are limited due to late diagnosis in the majority of the cases, metastatic spread to the peritoneal cavity and the onset of chemo-resistance. Thus, novel therapeutic methods are required. Statins and amino-bisphosphonates are inhibitors of the mevalonate pathway, which is a fundamental pathway of cellular metabolism, essential for cholesterol production and posttranslational protein farnesylation and geranylgeranylation. While this pathway has emerged as a encouraging treatment target in several human malignancies, its potential as a therapeutic approach in.