Virtual Library
Start Your Search
Tomoko Warita
Author of
-
+
P62 - Tumor Biology and Systems Biology - Basic and Translational Science - Metabolomics (ID 200)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P62.06 - The Consideration of Effects of Statin on Metabolism in Statin-Resistant Cells and Statin-Sensitive Cells (ID 1811)
00:00 - 00:00 | Presenting Author(s): Tomoko Warita
- Abstract
Introduction
The anticancer action of statins, which are blood cholesterol-lowering drugs called HMG-CoA reductase inhibitors, has drawn much attention from the perspective of drug repositioning. However, it is unclear that what kind of cancer cells are affected by the statins. Here, we performed metabolome analysis using two lung cancer cells (NCI-H322M; statin-resistant cells, HOP-92; statin-sensitive cells), and tried to select metabolites useful for screening for statin-sensitive cancers.
Methods
Metabolites in atorvastatin-treated cells were extracted by methanol, and ultrafiltered samples were analyzed by capillary electrophoresis mass spectrometry (CE-MS). Final concentrations of atorvastatin were 0.1 μM and 1 μM for HOP-92 cells, and 1 μM and 10 μM for NCI-H322M cells.
Results
A major characteristic of statin-treated HOP-92 cells was an effect on glycolysis. The amount of intracellular Glucose-6-Phosphate (G6P) and Fructose-6-Phosphate (F6P), which are substances produced in the early stages of glycolysis, showed no change with or without statin-treatment; however, the amount of downstream metabolites such as Fructose-1,6-diphosphate (F1,6P) and Glyceraldehyde-3-phosphate (G3P) were decreased by atorvastatin in a dose-dependent manner. It was suggested that phosphofructokinase may be affected in statin-sensitive cancer cells. In order to clarify the difference in response to statin-treatment between NCI-H322M and HOP-92, ratio of mean value on metabolites was calculated ([1 μM statin-treatment] / [0 μM statin-treatment]). As a result, in NCI-H322M cells, glucose uptake was not suppressed by statin, and F1,6P also maintained a high value. On the other hand, glucose uptake of HOP-92 cells was affected by statins, and it was considered that central carbon metabolism including glycolysis was downregulated.
Conclusion
From these results, it was suggested that the possibility of the differences of glucose uptake and of phosphofructokinase activity between statin-resistant cells and statin-sensitive cells.
-
+
P72 - Tumor Biology and Systems Biology - Basic and Translational Science - Tumor Microenvironment (ID 211)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P72.04 - Statin Counteracts Cell Proliferation and EMT-Induction in NCI-H322M Cells Treated with TGF-β (ID 1485)
00:00 - 00:00 | Author(s): Tomoko Warita
- Abstract
Introduction
Statins, the cholesterol lowering drugs, are known to exert anticancer effects on mesenchymal cancer cells. Epithelial cancer cells have been known to undergo epithelial-mesenchymal transition (EMT) with the increasing malignant potential. Transforming growth factor-β (TGF-β) induces EMT, and epithelial cancer cells gain characteristics of mesenchymal cells; however, the relationship between TGF-β-induced EMT and the anti-cancer effects of statins is not well understood. In this study, we examined the effect of statin-pretreatment on TGF-β-treated NCI-H322M cells, the epithelial lung cancer cell line.
Methods
Bronchoalveolar adenocarcinoma-derived NCI-H322M cells was used in this study. The culture medium was changed to new serum-starved medium (0.5% FBS) supplemented with 10 ng/mL of TGF-β1 and 0–5 µM of atorvastatin. To maintain optimal culture conditions, the serum-starved medium containing TGF-β1 and atorvastatin was replaced every three days, and after 6 days incubation, the cell number was counted. Total RNA and protein were also extracted from the duplicated samples. The EMT was confirmed based on expression changes of epithelial markers (E-cadherin) and mesenchymal markers (Vimentin and N-cadherin).
Results
As the concentration of atorvastatin increased, the cell number of TGF-β1 (+) groups significantly decreased compared to same dosage of atorvastatin-treated TGF (-) groups (P <0.01). TGF-β1-induced upregulation of N-cadherin expression was strongly inhibited by increased concentration of atorvastatin both at the mRNA and protein level.
Conclusion
TGF-β induced EMT improves atorvastatin's growth inhibitory effect in the NCI-H322M cell line. In addition, the pretreatment of statin strongly inhibits TGF-β-induced upregulation of N-cadherin, the protein which expression in tumor cells induces increased motility, invasion, and metastasis.
