Differential effects of pravastatin and simvastatin on the growth of tumor cells from different organ sites.
Differential effects of pravastatin and simvastatin on the growth of tumor cells from different organ sites.
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DOI：
10.1371/journal.pone.0028813
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Krishnan K
中科院分区：
文献类型：
--
作者：
Menter DG;Ramsauer VP;Harirforoosh S;Chakraborty K;Yang P;Hsi L;Newman RA;Krishnan K
3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 抑制剂，通常称为他汀类药物，可能具有癌症预防和治疗特性。他汀类药物是胆固醇合成的有效抑制剂，在预防心血管疾病方面具有明确的风险效益比。从机制上讲，靶向 HMGCR 活性主要影响胆固醇生物合成和信号蛋白的异戊二烯化。普伐他汀是一种亲水性他汀类药物，可被仅在肝脏中表达的不依赖于钠的有机阴离子转运蛋白 1B1 (OATP1B1) 选择性吸收。辛伐他汀是一种疏水性他汀类药物，可通过其他机制进入细胞。从不同组织中选择低分化和高分化癌细胞系，并检查它们对这两种他汀类药物的反应。辛伐他汀比普伐他汀更有效地抑制大多数肿瘤细胞系的生长，且呈剂量依赖性。低分化癌细胞通常比高分化癌细胞对辛伐他汀更敏感，并且 HMGCR 表达水平与他汀类药物治疗的反应并不一致。普伐他汀由于促进摄取而对正常肝细胞具有显着影响，但由于 OATP1B1 mRNA 和蛋白仅在正常肝脏和肝细胞中发现，因此对前列腺 PC3 和结肠 Caco-2 癌细胞影响较小。细胞生长的抑制伴随着线粒体网络的明显改变以及与肌动蛋白丝切蛋白调节和 p-caveolin 丧失相关的细胞形态的巨大变化。他汀类药物（亲水性普伐他汀和疏水性辛伐他汀）都会导致 OATP1B1 和 HMGCR 重新分布到核周位点。总之，不同类别他汀类药物的具体化学性质决定了在评估对他汀类药物的生物反应时可能相关的机械性质。
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, commonly known as statins, may possess cancer preventive and therapeutic properties. Statins are effective suppressors of cholesterol synthesis with a well-established risk-benefit ratio in cardiovascular disease prevention. Mechanistically, targeting HMGCR activity primarily influences cholesterol biosynthesis and prenylation of signaling proteins. Pravastatin is a hydrophilic statin that is selectively taken up by a sodium-independent organic anion transporter protein-1B1 (OATP1B1) exclusively expressed in liver. Simvastatin is a hydrophobic statin that enters cells by other mechanisms. Poorly-differentiated and well-differentiated cancer cell lines were selected from various tissues and examined for their response to these two statins. Simvastatin inhibited the growth of most tumor cell lines more effectively than pravastatin in a dose dependent manner. Poorly-differentiated cancer cells were generally more responsive to simvastatin than well-differentiated cancer cells, and the levels of HMGCR expression did not consistently correlate with response to statin treatment. Pravastatin had a significant effect on normal hepatocytes due to facilitated uptake and a lesser effect on prostate PC3 and colon Caco-2 cancer cells since the OATP1B1 mRNA and protein were only found in the normal liver and hepatocytes. The inhibition of cell growth was accompanied by distinct alterations in mitochondrial networks and dramatic changes in cellular morphology related to cofilin regulation and loss of p-caveolin. Both statins, hydrophilic pravastatin and hypdrophobic simvastatin caused redistribution of OATP1B1 and HMGCR to perinuclear sites. In conclusion, the specific chemical properties of different classes of statins dictate mechanistic properties which may be relevant when evaluating biological responses to statins.
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影响因子：
6
作者：
Li, YC;Park, MJ;Kim, YN
通讯作者：
Kim, YN
DOI：
10.1016/0005-2760(90)90139-o
发表时间：
1990-07-16
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
KOGA, T;SHIMADA, Y;YAMAZAKI, M
通讯作者：
YAMAZAKI, M
影响因子：
4.5
作者：
Hagenbuch, B;Meier, PJ
通讯作者：
Meier, PJ
影响因子：
3.5
作者：
ENDO, A;KURODA, M;TANZAWA, K
通讯作者：
TANZAWA, K
DOI：
10.1016/j.jchromb.2004.11.014
发表时间：
2005-02-25
影响因子：
3
作者：
Kawabata, K;Samata, N;Urasaki, Y
通讯作者：
Urasaki, Y