| RRC ID |
52498
|
| 著者 |
Kaji K, Nishimura N, Seki K, Sato S, Saikawa S, Nakanishi K, Furukawa M, Kawaratani H, Kitade M, Moriya K, Namisaki T, Yoshiji H.
|
| タイトル |
Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake.
|
| ジャーナル |
Int J Cancer
|
| Abstract |
Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells. Canagliflozin exerted antiproliferative effects on SGLT2-expressing Huh7 and HepG2 cells in a dose-dependent manner by inhibiting glycolytic metabolism including glucose uptake, lactate and intracellular ATP production. This agent also induced G2/M arrest and apoptosis with inhibited phosphorylation of ERK, p38 and AKT and cleavage of caspase3. Xenograft tumor growth assay showed that oral administration of canagliflozin (10 mg/kg/day) significantly reduced subcutaneous tumor burdens in a glycemic status-independent manner, and attenuated intratumor vascularization in Huh7- and HepG2-derived xenograft tumors in BALB/c nude mice. In vitro, canagliflozin suppressed the increased human umbilical vein endothelial cell (HUVEC) proliferation and tubular formation which were observed in Huh7 or HepG2 co-cultures. By contrast, canagliflozin had no effect on tumor growth and intratumor angiogenesis in SGLT2-null HLE-derived xenograft models. These results indicate that SGLT2-I therapy is a potential new strategy for the treatment of HCC.
|
| 巻・号 |
142(8)
|
| ページ |
1712-1722
|
| 公開日 |
2018-4-15
|
| DOI |
10.1002/ijc.31193
|
| PMID |
29205334
|
| MeSH |
Angiogenesis Inhibitors / pharmacology*
Animals
Antineoplastic Agents / pharmacology
Canagliflozin / pharmacology*
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Coculture Techniques / methods
G2 Phase Cell Cycle Checkpoints / drug effects
Glucose / metabolism*
Hep G2 Cells
Human Umbilical Vein Endothelial Cells
Humans
Liver / drug effects
Liver / metabolism
Liver Neoplasms / drug therapy*
Liver Neoplasms / metabolism*
Mice
Mice, Inbred BALB C
Mice, Nude
Neovascularization, Physiologic / drug effects
Sodium-Glucose Transporter 2
Sodium-Glucose Transporter 2 Inhibitors*
|
| IF |
5.145
|
| 引用数 |
21
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2(RCB1886) |
