Retrovirus‐mediated transfer of the herpes simplex virus thymidine kinase and connexin26 genes in pancreatic cells results in variable efficiency on the bystander killing: Implications for gene therapy
Retrovirus‐mediated transfer of the herpes simplex virus thymidine kinase and connexin26 genes in pancreatic cells results in variable efficiency on the bystander killing: Implications for gene therapy
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逆转录病毒介导的单纯疱疹病毒胸苷激酶和连接蛋白26基因在胰腺细胞中的转移导致旁观者杀伤效率的变化：对基因治疗的影响
DOI：
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发表时间：
2001
影响因子：
6.4
通讯作者：
C. Fillat
中科院分区：
文献类型：
--
作者：
M. Carrió;A. Mazo;C. López;X. Estivill;C. Fillat
目前，胰腺癌没有有效的治疗方法，单纯疱疹病毒胸苷激酶基因（HSV-tk）联合更昔洛韦（GCV）的前药激活基因疗法已被建议作为对抗这种疾病的候选方法。在本研究中，我们评估了HSV-tk/GCV治疗在一组胰腺肿瘤细胞（NP-9、NP-18、NP-31）中的疗效，以及与连接蛋白26基因（Cx 26）过表达相结合的细胞毒性作用的增强。用含有HSV-tk基因的逆转录病毒转导的胰腺细胞显示出对GCV的不同敏感性，这似乎与HSV-tk表达水平无关。旁观者效应的程度在胰腺癌细胞中也不同，并与间隙连接细胞间通讯（GJIC）水平相关。用携带连接蛋白26基因的逆转录病毒转导胰腺肿瘤细胞导致连接蛋白26的高水平表达和GJIC的增加，这与NP-9 Cx 26和NP-18 Cx 26细胞中的旁观者效应在一定程度上相关。在NP-31 Cx 26中未检测到GJIC增加或旁观者杀伤增加。NP-18 Cx 26细胞中的旁观者效应也被GJIC的长期抑制剂18-α-大黄酸（阿加）阻止。总之，这些结果表明胰腺肿瘤细胞在对HSV-tk/GCV治疗的敏感性方面存在高度差异。此外，他们指出，Cx 26基因的过度表达并不总是对应于GJIC的增加，尽管他们清楚地表明GJIC在介导旁观者效应中的作用。© 2001 Wiley利斯公司
Currently, there is no effective treatment for pancreatic cancer and prodrug‐activating gene therapy with the herpes simplex virus thymidine kinase gene (HSV‐tk) in combination with ganciclovir (GCV) has been suggested as a candidate approach against this disease. In the present study, we have evaluated the efficacy of the HSV‐tk/GCV treatment in a panel of pancreatic tumor cells (NP‐9, NP‐18, NP‐31) and the potentiation of the cytotoxic effect in combination with the overexpression of the connexin 26 gene (Cx26). Pancreatic cells transduced with a retrovirus containing the HSV‐tk gene showed different sensitivities to GCV that seemed to be independent of HSV‐tk expression levels. The extent of the bystander effect also varied among the pancreatic tumor cells and correlated with the level of gap junction intercellular communication (GJIC). Transduction of the pancreatic tumor cells with a retrovirus carrying the connexin 26 gene resulted in high levels of connexin 26 expression and in an increase in the GJIC that correlated to an extent in the bystander effect in both NP‐9Cx26 and NP‐18Cx26 cells. Neither an increment in GJIC nor an increase in the bystander killing was detected in NP‐31Cx26. The bystander effect in NP‐18 Cx26 cells was also prevented by the long term inhibitor of GJIC, 18‐α‐glycyrrhetinic acid (AGA). Together, these results demonstrate that pancreatic tumor cells are highly different as regards the susceptibility to HSV‐tk/GCV treatment. Moreover, they indicate that overexpression of the Cx26 gene does not always correspond to an increase in GJIC although they clearly suggest the role of GJIC in mediating the bystander effect. © 2001 Wiley‐Liss, Inc.
单纯疱疹病毒胸苷激酶/更昔洛韦介导的旁观者细胞凋亡。
DOI：
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发表时间：
1996
期刊：
Cancer research.
影响因子：
--
作者：
Hamel,W;Magnelli,L;Chiarugi,VP;Israel,MA
通讯作者：
Israel,MA
DOI：
10.1073/pnas.80.9.2767
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHENG, YC;HUANG, ES;GRILL, SP
通讯作者：
GRILL, SP
体内胰腺癌的定向酶前体药物基因治疗。
影响因子：
3.8
作者：
DiMaio,JM;Clary,BM;Via,DF;Coveney,E;Pappas,TN;Lyerly,HK
通讯作者：
Lyerly,HK