Kim Ki Young, Kim Sung Soo, Cheon Hyae Gyeong
Bioorganic Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Republic of Korea.
Biochem Pharmacol. 2006 Aug 28;72(5):530-40. doi: 10.1016/j.bcp.2006.05.009. Epub 2006 Jun 27.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation has been a new approach to cancer therapy. In the present study, we investigated the effects of two structurally different PPARgamma agonists, rosiglitazone and KR-62980 on MCF-7 breast cancer cells. Both agonists inhibited the cell proliferation and colony formation via apoptosis. PTEN expression was increased with decreased Akt phosphorylation by the agonists, whereas agonists actions were abolished in PTEN knockdown cells, indicating the critical role of PTEN in the anti-proliferative effects of PPARgamma activation. Rosiglitazone induced the MCF-7 cell differentiation but KR-62980 did not alter the differentiation pattern with little effects on the lipid accumulation and the expression of lipogenesis markers. These results suggest that PPARgamma activation may result in the inhibition of cell proliferation and/or induction of cell differentiation depending on the type of PPARgamma agonists, and that KR-62980 may be useful in breast cancer therapy by inducing apoptosis.
过氧化物酶体增殖物激活受体γ（PPARγ）激活已成为癌症治疗的一种新方法。在本研究中，我们研究了两种结构不同的PPARγ激动剂罗格列酮和KR - 62980对MCF - 7乳腺癌细胞的影响。两种激动剂均通过凋亡抑制细胞增殖和集落形成。激动剂使PTEN表达增加，Akt磷酸化减少，而在PTEN基因敲低的细胞中激动剂的作用消失，表明PTEN在PPARγ激活的抗增殖作用中起关键作用。罗格列酮诱导MCF - 7细胞分化，但KR - 62980未改变分化模式，对脂质积累和脂肪生成标志物的表达影响很小。这些结果表明，PPARγ激活可能根据PPARγ激动剂的类型导致细胞增殖抑制和/或细胞分化诱导，并且KR - 62980可能通过诱导凋亡在乳腺癌治疗中有用。
