Fujiwara Kimiko, Tsubaki Masanobu, Yamazoe Yuzuru, Nishiura Saori, Kawaguchi Takeru, Ogaki Mitsuhiko, Nishinobo Minori, Shimamoto Kenji, Moriyama Kenzo, Nishida Shozo
Department of Pharmacy, Kinki University Hospital, Osakasayama City, Japan.
Yakugaku Zasshi. 2008 Jan;128(1):153-8. doi: 10.1248/yakushi.128.153.
Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, suppress cell proliferation and induce apoptosis in various cancer cell lines. However, the effects of statins in head and neck carcinoma have not been reported. In this study, we investigated the mechanism by which fluvastatin induces apoptosis in HSC-3 cells. An increase in caspase-3 activity was observed. The apoptosis induced by fluvastatin was inhibited by the addition of geranylgeranyl pyrophosphate (GGPP) to the cell culture. When we examined the survival signals at the time of apoptotic induction, we also found that fluvastatin had caused a remarkable decrease in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Moreover, we also found that U0126, a MEK1/2 inhibitor, induces apoptosis in HSC-3 cells. These results suggested that fluvastatin induces apoptosis by inhibiting GGPP biosynthesis and consequently decreasing the level of phosphorylated ERK1/2. The results of this study also indicate that fluvastatin may be used as an anticancer agent for tongue carcinoma.
他汀类药物是3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的抑制剂，可抑制多种癌细胞系的细胞增殖并诱导其凋亡。然而，他汀类药物对头颈部癌的作用尚未见报道。在本研究中，我们探究了氟伐他汀诱导HSC-3细胞凋亡的机制。观察到半胱天冬酶-3活性增加。向细胞培养物中添加香叶基香叶基焦磷酸（GGPP）可抑制氟伐他汀诱导的凋亡。当我们检测凋亡诱导时的存活信号时，还发现氟伐他汀导致细胞外信号调节激酶（ERK）1/2的磷酸化显著降低。此外，我们还发现MEK1/2抑制剂U0126可诱导HSC-3细胞凋亡。这些结果表明，氟伐他汀通过抑制GGPP生物合成并因此降低磷酸化ERK1/2的水平来诱导凋亡。本研究结果还表明，氟伐他汀可能用作舌癌的抗癌剂。
