Delivery of PTEN via a novel gene microcapsule sensitizes prostate cancer cells to irradiation

作者：Tomioka Atsushi; Tanaka Motoyoshi^*; De Velasco Marco A; Anai Satoshi; Takada Satoshi; Kushibiki Toshihiro; Tabata Yasuhiko; Rosser Charles J; Uemura Hirotsugu; Hirao Yoshihiko

来源：Molecular Cancer Therapeutics, 2008, 7(7): 1864-1870.

DOI：10.1158/1535-7163.MCT-07-2198

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.

• 出版日期2008-7