Delivery of PTEN via a novel gene microcapsule sensitizes prostate cancer cells to irradiation.
The tumor suppressor gene MMAC/PTEN located on chromosome10q23.3 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.
Tomioka
Atsushi
A
Department of Urology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Tanaka
Motoyoshi
M
De Velasco
Marco A
MA
Anai
Satoshi
S
Takada
Satoshi
S
Kushibiki
Toshihiro
T
Tabata
Yasuhiko
Y
Rosser
Charles J
CJ
Uemura
Hirotsugu
H
Hirao
Yoshihiko
Y
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002214:Capsules; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
D002214:Capsules; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human