Enhancement of the anti-tumor effect of 5'-deoxy-5-fluorouridine by transfection of thymidine phosphorylase gene into human colon cancer cells.
Enhancement of the anti-tumor effect of 5'-deoxy-5-fluorouridine by transfection of thymidine phosphorylase gene into human colon cancer cells.
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DOI：
10.1111/j.1349-7006.1999.tb00769.x
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发表时间：
1999-04
期刊：
影响因子：
--
通讯作者：
Monden M
中科院分区：
文献类型：
--
作者：
Kanyama H;Tomita N;Yamano T;Miyoshi Y;Ohue M;Fujiwara Y;Sekimoto M;Sakita I;Tamaki Y;Monden M
胸苷磷酸化酶(DThdPase)是一种将5‘-脱氧-5-氟尿苷(5’-DFUR)转化为毒性物质5-氟尿嘧啶(5-FU)的酶，也被认为是一种血小板衍生的内皮细胞生长因子。为探讨5‘DFUR与转化酶dThdPase联合应用于结直肠癌自杀基因治疗的可行性，我们将dThdPase基因导入人结肠癌细胞系SW480，并对其生长方式及对5-FU或5’DFUR的敏感性进行了分析。5-FU对亲本细胞、对照载体转染组和dThdPase转染组细胞的半数抑制率(IC50值)分别为4.9、6.3和2.9μM。SW480/dThdPase的IC50低于SW480或SW480/V1，但差异无统计学意义。5‘DFUR对SW480、SW480/V1和SW480/dThdPase的IC50值分别约为300、330和3.2αM。与SW480或SW480/V1相比，SW480/dThdPase对5‘DFUR的敏感性提高了约100倍。在10%的转染率下，该系统对5‘-DFUR具有足够高的抑制细胞生长的敏感性，表明该系统具有较强的旁观者效应。S.C.在体内的生长。腹腔注射能显著抑制SW480/dThdPase裸鼠移植瘤的生长。注射5‘DFUR与接受磷酸盐缓冲盐水(PBS)处理的对照小鼠进行比较。这些结果表明，5‘DFUR和dThdPase基因联合治疗结肠癌可能是一种有用的方法。
Thymidine phosphorylase (dThdPase) is an enzyme that converts 5′‐deoxy‐5‐fluorouridine (5′DFUR) to the toxic substance 5‐fluorouracil (5‐FU); it is also known to be a platelet‐derived endothelial cell growth factor. In order to investigate the feasibility of suicide gene therapy against colorectal cancer by means of the combination of 5′DFUR and the converting enzyme dThdPase, we transfected the dThdPase gene into the human colon cancer cell line SW480 and analyzed the growth pattern as well as the sensitivity to 5‐FU or 5′DFUR of the dThdPase‐transfected cells. The 50% inhibition (IC50) values of 5‐FU against the SW480 parental cells, control vector‐transfected cells SW480/V1, and dThdPase‐transfected cells SW480/dThdPase were approximately 4.9, 6.3, and 2.9 μM, respectively. The IC50 of SW480/dThdPase was lower than that of SW480 or SW480/V1, although the differences were not statistically significant. The IC50 values of 5′DFUR for SW480, SW480/V1, and SW480/dThdPase were approximately 300, 330, and 3.2 αM, respectively. The sensitivity to 5′DFUR of SW480/dThdPase was increased by about 100‐fold compared with that of SW480 or SW480/V1. With only 10% transfection efficacy, a high enough sensitivity to 5′DFUR was obtained to suppress the cell growth, indicating that a strong bystander effect was induced by this system. The in vivo growth of the s.c. transplanted SW480/dThdPase tumor in nude mice was significantly suppressed by i.p. injection of 5′DFUR compared with that in control mice that received phosphate‐buffered saline (PBS) treatment. These results suggest that gene therapy using the combination of 5′DFUR and the dThdPase gene may be a useful approach for treatment of colon cancer.
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影响因子：
1.7
作者：
ISHIYAMA, M;SHIGA, M;HE, PG
通讯作者：
HE, PG
影响因子：
15.9
作者：
MARSH, JC;PERRY, S
通讯作者：
PERRY, S
DOI：
10.1016/0027-5107(88)90075-9
发表时间：
1988-07-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
SHAW, T;SMILLIE, RH;MACPHEE, DG
通讯作者：
MACPHEE, DG
影响因子：
8.8
作者：
Patterson, A V;Zhang, H;Moghaddam, A;Bicknell, R;Talbot, D C;Stratford, I J;Harris, A L
通讯作者：
Harris, A L
影响因子：
6.4
作者：
LUCCIONI, C;BEAUMATIN, J;LEFRANCOIS, D
通讯作者：
LEFRANCOIS, D