The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo

Yuanhong Gao, Hiromichi Ishiyama, Mianen Sun, Kathryn L. Brinkman, Xiaozhen Wang, Julie Zhu, Weiyuan Mai, Ying Huang, Daniel Floryk, Michael Ittmann, Timothy C. Thompson, E. B. Butler, Bo Xu, Bin S. Teh

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Perifosine is a membrane-targeted alkylphospholipid developed to inhibit the PI3K/Akt pathway and has been suggested as a favorable candidate for combined use with radiotherapy. In this study, we investigated the effect of the combined treatment of perifosine and radiation (CTPR) on prostate cancer cells in vitro and on prostate cancer xenografts in vivo.Methods: Human prostate cancer cell line, CWR22RV1, was treated with perifosine, radiation, or CTPR. Clonogenic survival assays, sulforhodamine B cytotoxity assays and cell density assays were used to assess the effectiveness of each therapy in vitro. Measurements of apoptosis, cell cycle analysis by flow cytometry and Western blots were used to evaluate mechanisms of action in vitro. Tumor growth delay assays were used to evaluate radiation induced tumor responses in vivo.Results: In vitro, CTPR had greater inhibitory effects on prostate cancer cell viability and clonogenic survival than either perifosine or radiation treatment alone. A marked increase in prostate cancer cell apoptosis was noted in CTPR. Phosphorylation of AKT-T308 AKT and S473 were decreased when using perifosine treatment or CTPR. Cleaved caspase 3 was significantly increased in the CTPR group. In vivo, CTPR had greater inhibitory effects on the growth of xenografts when compared with perifosine or radiation treatment alone groups.Conclusions: Perifosine enhances prostate cancer radiosensitivity in vitro and in vivo. These data provide strong support for further development of this combination therapy in clinical studies.

Original languageEnglish (US)
Article number38
JournalRadiation Oncology
Volume6
Issue number1
DOIs
StatePublished - Apr 15 2011

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo'. Together they form a unique fingerprint.

Cite this