法國國家科研中心28日發(fā)表公報說，法國、澳大利亞和英國研究人員發(fā)現(xiàn)一種新的分子，不僅可以遏制癌細胞增殖,，還能抑制其流動性，防止癌細胞轉(zhuǎn)移,。
惡性腫瘤細胞對化療產(chǎn)生抗藥性是導(dǎo)致傳統(tǒng)化療失敗的一個重要因素,，癌細胞轉(zhuǎn)移也是造成患者死亡最普遍的原因。鑒于此,，由法,、澳、英三國研究人員組成的團隊近十年來一直在尋找新的有效藥物,，阻止癌細胞轉(zhuǎn)移形成新的病灶,。
研究人員通過一個高通量自動化篩選平臺對近3萬種分子進行篩選，希望能找到具有抗癌性和抗轉(zhuǎn)移性的分子,。最終,，他們在法國居里研究所的分子庫里找到了一種名為Liminib的分子，這種分子對LIM激酶具有抑制作用。而LIM激酶能夠調(diào)節(jié)細胞骨架的活性,，在癌細胞的侵襲和轉(zhuǎn)移過程中發(fā)揮重要作用,。
據(jù)稱，Liminib分子是目前發(fā)現(xiàn)的首種LIM激酶抑制劑,，它和目前廣泛使用的抗癌藥物紫杉醇作用機制不同,，是通過破壞肌動蛋白的細胞骨架來阻止癌細胞擴散和轉(zhuǎn)移。對小鼠模型的實驗也表明,，它對多種癌細胞具有殺傷力,。
研究人員認為，人們有望在將來利用這種分子開發(fā)出新的癌癥治療方法,。相關(guān)研究成果已經(jīng)發(fā)表在《癌癥研究》雜志上,。（生物谷Bioon.com）
doi: 10.1158/0008-5472.CAN-11-3342
PMC:
PMID:
Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth
Renaud Prudent, Emilie Vassal-Stermann, Chi-Hung Nguyen, Catherine Pillet, Anne Martinez, Chloé Prunier, Caroline Barette, Emmanuelle Soleilhac, Odile Filhol, Anne Beghin, Glaucio Valdameri, Stéphane Honoré, Samia Aci-Sèche, David Grierson, Juliana Antonipillai, Rong Li, Attilio Di Pietro, Charles Dumontet, Diane Braguer, Jean-Claude Florent, Stefan Knapp, Ora Bernard and Laurence Lafanechère
The emergence of tumor resistance to conventional microtubule-targeting drugs restricts their clinical use. Using a cell-based assay that recognizes microtubule polymerization status to screen for chemicals that interact with regulators of microtubule dynamics, we identified Pyr1, a cell permeable inhibitor of LIM kinase, which is the enzyme that phosphorylates and inactivates the actin-depolymerizing factor cofilin. Pyr1 reversibly stabilized microtubules, blocked actin microfilament dynamics, inhibited cell motility in vitro and showed anticancer properties in vivo, in the absence of major side effects. Pyr1 inhibition of LIM kinase caused a microtubule-stabilizing effect, which was independent of any direct effects on the actin cytoskeleton. In addition, Pyr1 retained its activity in multidrug-resistant cancer cells that were resistant to conventional microtubule-targeting agents. Our findings suggest that LIM kinase functions as a signaling node that controls both actin and microtubule dynamics. LIM kinase may therefore represent a targetable enzyme for cancer treatment.
