亲吻素10通过Smad信号通路抑制乳腺癌的瓦伯格效应：体内外实验均是如此。
Kisspeptin 10 inhibits the Warburg effect in breast cancer through the Smad signaling pathway: both in vitro and in vivo.
作者信息
Song Guo-Qing, Zhao Yi
机构信息
Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University 36 Sanhao Street, Heping, Shenyang, Liaoning 110004, P.R. China.
出版信息
Am J Transl Res. 2016 Jan 15;8(1):188-95. eCollection 2016.
Breast cancer is the most frequently diagnosed cancer in females. Warburg effect could enhance tumorigenesis and has garnered attention as a target for tumor treatment. In this study, we found that the mRNA and protein levels of hexokinase 2 (HK2), pyruvate kinase (PKM2), and pyruvate dehydrogenase kinase (PDK1) in breast cancer tissues were higher than those in corresponding noncancerous tissues. HK2, PKM2, and PDK1 expression was correlated statistically with the survival rate of the patients with breast cancer. We also demonstrated a shorter fragment of KISS1, Kisspeptin-10 (KP-10), inhibited the Warburg effect and induced mitochondrial injury in human breast cancer cell line, MDA-MB-231. We confirmed that KP-10-inhibited the Warburg effect by activating Smad pathway. The effects and related mechanisms of these treatments were also confirmed in murine xenografts. However, additional studies are needed to confirm these results in other cell types.
乳腺癌是女性中最常被诊断出的癌症。瓦伯格效应可增强肿瘤发生，并作为肿瘤治疗靶点受到关注。在本研究中，我们发现乳腺癌组织中己糖激酶2（HK2）、丙酮酸激酶（PKM2）和丙酮酸脱氢酶激酶（PDK1）的mRNA和蛋白质水平高于相应的癌旁组织。HK2、PKM2和PDK1的表达与乳腺癌患者的生存率具有统计学相关性。我们还证明，KISS1的较短片段，即亲吻素-10（KP-10），可抑制人乳腺癌细胞系MDA-MB-231中的瓦伯格效应并诱导线粒体损伤。我们证实，KP-10通过激活Smad通路抑制瓦伯格效应。这些治疗的效果和相关机制也在小鼠异种移植模型中得到了证实。然而，需要进一步研究以在其他细胞类型中证实这些结果。
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