Delivery of PTEN via a novel gene microcapsule sensitizes prostate cancer cells to irradiation
Delivery of PTEN via a novel gene microcapsule sensitizes prostate cancer cells to irradiation
复制标题
DOI：
10.1158/1535-7163.mct-07-2198
复制
发表时间：
2008-07-01
影响因子：
5.7
通讯作者：
Hirao, Yoshihiko
中科院分区：
文献类型：
--
作者：
Tomioka, Atsushi;Tanaka, Motoyoshi;Hirao, Yoshihiko
位于染色体10q23.3上的肿瘤抑制基因MMAC/PTEN在磷酸肌醇-3-激酶信号通路中具有双重磷酸酶活性，并抑制Akt活化，Akt是一种丝氨酸-苏氨酸激酶，其参与增殖和抗凋亡通路。此外，MMAC/PTEN在包括前列腺癌在内的多种肿瘤中经常失活。在这项研究中，我们产生了一种新型的基因转移药物，GelaTen：这是一个微球的阳离子化明胶水凝胶纳入PTEN质粒DNA。使用我们先前报道的抗辐射的PC 3-Bcl-2人前列腺癌细胞（PTEN缺失），我们检查了GelaTen在单独或与辐射一起瘤内注射后迫使PTEN在体内表达以抑制肿瘤生长的功效。与GelaTen或单独照射相比，GelaTen和照射的组合治疗改善了生长抑制的体外和体内功效。这些数据表明，GelaTen基因疗法，使放射增敏，可以潜在地治疗前列腺癌，具有与放射抗性相关的MMAC/PTEN基因改变。
The tumor suppressor gene MMAC/PTEN located on chromosome 10q23.3 has dual phosphatase activity in the phosphoinositide-3-kinase signaling pathway and inhibits Akt activation, a serine-threonine kinase, which is involved in proliferative and antiapoptotic pathways. Furthermore, MMAC/PTEN is frequently inactivated in a variety of tumors including prostate cancer. In this study we generated a new type of gene transfer drug, GelaTen: which is a microsphere of cationized gelatin hydrogels incorporating PTEN plasmid DNA. Using our previously reported radiation-resistant PC3-Bcl-2 human prostate cancer cells (PTEN deleted), we examined the efficacy of GelaTen to force the expression of PTEN in vivo to inhibit tumor growth after intratumoral injection alone or with irradiation. Combinational therapy with GelaTen and irradiation improved both the in vitro and in vivo efficacy of growth inhibition compared with GelaTen or irradiation alone. These data show that GelaTen gene therapy, enabling radiosensitization, can potentially treat prostate cancers that have MMAC/PTEN gene alterations associated with radioresistance.