摘要
OBJECTIVE: To investigate the antitumor and anti-metastatic effect of in situ transduction of adenovirus encoding cytosine deaminase (AdCD) followed by the systemic use of 5-fluorocytosine (5-FC) in the orthotopic (o.t.) prostate cancer mouse model. METHODS: The o.t. prostate cancer model of C57BL/6 mouse was developed by o.t. inoculation of RM-1 cells to the subcapsular area of the prostate gland. In situ transduction of the CD gene, followed by systemic use of 5-FC at a daily dosage of 300 mg/kg for 14 days, was performed two days later. RESULTS: Compared with mice treated with Adbeta-gal/5-FC, 5-FC and PBS, mice of the o.t. model receiving in situ treatment of AdCD/5-FC had significant prolongation of survival and suppression of local tumor growth. More importantly, pathological observations showed that metastatic activity occurred in all mice of the PBS, 5-FC and Adbeta-gal groups including metastasis to the iliac lymph node (10/10, 10/10, 10/10) and the lung (8/10, 7/10, 7/10). However, only two out of ten had iliac lymphatic metastasis in the AdCD/5-FC group with no systemic or preaotic lymphatic metastasis, suggesting a strong metastatic inhibitory effect. CONCLUSIONS: In situ transduction of AdCD followed by systemic use of 5-FC leads to the inhibitory effect on tumor growth and metastatic activity in the o.t. mouse model of prostate cancer. Clinically, it may be possible to treat metastatic or recurrent prostate cancer with a novel gene therapy using in situ injection techniques in future.
目的 探讨原位CD基因转导配合全身应用 5 FC对于前列腺癌原位移植瘤模型肿瘤和转移的抑制作用。方法 通过向C5 7BL/6小鼠的前列腺包膜下原位接种前列腺癌RM 1细胞建立前列腺癌原位移植瘤模型。两天后进行原位CD基因注射 ,腹腔注射 30 0mg/kg/天的 5 FC溶液共 14天。结果 与应用Adβ gal/5 FC ,5 FC和PBS的三组比较 ,接受原位CD基因转导配合全身应用 5 FC治疗的荷瘤鼠存活时间明显延长 ,局部肿瘤的生长受到明显抑制。更重要的是 ,病理学观察发现原位模型中的PBS、5 FC和Adβ gal三组小鼠全部发生肿瘤转移 ,包括髂淋巴结的转移 (10 /10 ,10 /10 ,10 /10 )和肺转移 (8/10 ,7/10 ,7/10 ) ,而AdCD/5 FC治疗组中肿瘤转移的发生机率仅为 2 /10 ,且均为髂淋巴结的转移 ,而各主要脏器及腹主动脉旁淋巴结均无转移发生 ,结果提示这一治疗方法具有很强的抗肿瘤转移作用。结论 原位CD基因转导配合全身应用 5 FC对于前列腺癌原位移植瘤模型的肿瘤和转移具有抑制作用。未来对于各种复发性或转移性的前列腺癌通过局部注射法作基因转导可能是一种新型的治疗方法。
