法國研究人員15日公布的研究報告顯示，人們可以用一種分子“誘餌”,，模擬脫氧核糖核酸（DNA）受損,，進而促使癌細胞自殺。
醫(yī)生經常用化學療法和放射性療法破壞癌細胞,，進而引起程序性細胞死亡,。然而，一些時候,，這些療法給癌細胞造成的破壞程度不足以激起程序性細胞死亡，而幸存下的癌細胞能自我修復,，使治療過程徒勞無功,。
為對付這種情況，法國巴黎居里研究所瑪麗·杜特萊斯帶領研究人員造出微小的DNA片斷,，模仿遺傳密碼雙螺旋結構兩端受損,，使那些頑固的癌細胞認為它們受損嚴重，進而“自殺”,，也就是程序性死亡,。
這一研究成果發(fā)表在最新一期美國《臨床癌癥研究》上,。研究人員說，一些惡性腫瘤對常規(guī)療法具有抵抗性,，這項研究為對付惡性腫瘤開辟了新道路,。
在老鼠身上做的實驗顯示，給老鼠用放射性療法前使用這種方法,，能消滅75%到100%的癌細胞,，而只用放射性療法，僅能摧毀30%到50%的癌細胞,。
杜特萊斯說,，如果一切進展順利，研究人員可能于2010年底開始在志愿者身上展開臨床實驗,。（生物谷Bioon.com）
生物谷推薦原始出處：
Clinical Cancer Research, 10.1158/1078-0432.CCR-08-2108
Small-Molecule Drugs Mimicking DNA Damage: A New Strategy for Sensitizing Tumors to Radiotherapy
Maria Quanz 1, 4, 5, Nathalie Berthault 1, 2, Christophe Roulin 4, Maryline Roy 1, 4, 5, Aurélie Herbette 1, 4, 5, Céline Agrario 1, 4, 5, Christophe Alberti 1, 3, Véronique Josserand 6, Jean-Luc Coll 6, Xavier Sastre-Garau 7, Jean-Marc Cosset 8, Lionel Larue 1, 3, Jian-Sheng Sun 5, 9, 10, 11, Marie Dutreix 1, 2, 4*
Authors' Affiliations: 1Institut Curie, Centre de Recherche; Centre National de la Recherche 2UMR2027 and 3UMR146; 4Institut Curie H?pital, Département de transfert, Orsay, France; 5DNA Therapeutics, Genopole, Evry, France; 6Institut National de la Santé et de la Recherche Médicale U578, La Tronche, France; and MD, Institut Curie H?pital, Departments of 7Pathology and 8Radiotherapy; 9Muséum National d'Histoire Naturelle, USM503; 10Institut National de la Santé et de la Recherche Médicale U565; 11Centre National de la Recherche, UMR5153, Paris, France
Purpose: Enhanced DNA repair activity is often associated with tumor resistance to radiotherapy. We hypothesized that inhibiting DNA damage repair would sensitize tumors to radiation-induced DNA damage.
Experimental Design: A novel strategy for inhibiting DNA repair was tested. We designed small DNA molecules that mimic DNA double-strand breaks (called Dbait) and act by disorganizing damage signaling and DNA repair. We analyzed the effects of Dbait in cultured cells and on xenografted tumors growth and performed preliminary studies of their mechanism(s) of action.
Results: The selected Dbait molecules activate H2AX phosphorylation in cell culture and in xenografted tumors. In vitro, this activation correlates with the reduction of Nijmegen breakage syndrome 1 and p53-binding protein 1 repair foci formation after irradiation. Cells are sensitized to irradiation and do not efficiently repair DNA damage. In vivo, Dbait induces regression of radioresistant head and neck squamous cell carcinoma (Hep2) and melanoma (SK28 and LU1205) tumors. The combination of Dbait32Hc treatment and fractionated radiotherapy significantly enhanced the therapeutic effect. Tumor growth control by Dbait molecules depended directly on the dose and was observed with various irradiation protocols. The induction of H2AX phosphorylation in tumors treated with Dbait suggests that it acts in vivo through the induction of "false" DNA damage signaling and repair inhibition.
Conclusions: These data validate the concept of introducing small DNA molecules, which mimic DNA damage, to trigger "false" signaling of DNA damage and impair DNA repair of damaged chromosomes. This new strategy could provide a new method for enhancing radiotherapy efficiency in radioresistant tumors.
