Molecular targeted gene therapy against hormone-refractoty prostate cancer by new ultrasonic gene transfection

点击翻译按钮获取中文摘要

Dihydropyrimidine dehydrogenase ( DPD ), an enzyme involved in metabolism of 5-fluorouracil ( 5-FU) , is a key factor determining the sensitivity of tumors to 5-FU. Therefore, it is critical to know in advance how much DPD the tumor expresses. DPD expression has been measured in several cancer tissues such as gastric cancer obtained clinically. However, the clinical significance of DPD expression in prostate cancer has never been reported. We investigated DPD expression in prostate cancer. We also determined whether 5-chloro-2, 4-dihydroxypyridine ( CDHP ), a potent inhibitor of DPD, enhanced the antitumoral activity of 5-FU against prostate cancer.Forty-four prostate tissue specimens were obtained form patients who underwent radical prostatectomy for prostate cancer without neoadjuvant hormonal therapy. We analyzed the cancerous tissue and normal prostate tissue for DPD expression using immunohistochemistry.The expression of DPD was significantly higher in prostate cancers compared with the normal prostate tissues. Thirty-six of 44 (82%) specimens of prostate cancer expressed DPD, whereas only twenty-five (57%) of 44 specimens of normal prostate tissue expressed DPD. DPD expression was significantly lower in prostate cancers patients who received neoadjuvant hormonal therapy. In vitro treatment with 5-FU/CDHP resulted in enhanced cytotoxicity compared with 5-FU alone treatment. In vivo, the size of DU145 tumors treated with oral administration of 5-FU and CDHP in mice was significantly smaller than that in mice receiving oral administration of 5-FU.The present study showed for the first time that the expression of DPD was highly detected in prostate cancer. In addition, DPD inhibitors may enhance the antitumor activity of 5-FU against prostate cancer.