Therapy of Smac mimetic SM-164 in combination with gemcitabine for pancreatic cancer.
Therapy of Smac mimetic SM-164 in combination with gemcitabine for pancreatic cancer.
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DOI：
10.1016/j.canlet.2012.10.039
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发表时间：
2013-02
期刊：
影响因子：
9.7
通讯作者：
Bin Zhou;Jie-shi Zhang;Ge Chen;L. You;Taiping Zhang;Yupei Zhao
中科院分区：
文献类型：
--
作者：
Bin Zhou;Jie-shi Zhang;Ge Chen;L. You;Taiping Zhang;Yupei Zhao
胰腺癌是一种对传统化疗耐药的恶性肿瘤。我们研究了SM-164和吉西他滨单独和联合治疗PC。PC细胞的存活率随着SM-164剂量的增加而降低。SM-164和/或吉西他滨增加了凋亡和死亡PC细胞的数量，以及caspase-3和PARP 1切割片段的表达，并抑制裸鼠中的肿瘤异种移植物生长。联合治疗的抑制作用比单药治疗更大，持续时间更长。无论是联合用药还是单药治疗，均未显示出任何显著的体内毒性。SM 164/吉西他滨处理小鼠的异种移植瘤组织中观察到细胞凋亡和坏死，Ki 67表达降低，以及裂解的caspase-3表达增加。SM-164与吉西他滨联合治疗PC可能是一种很有前途的新药物。
Pancreatic cancer (PC) is a lethal solid malignancy with resistance to traditional chemotherapy. We investigated therapy of PC with SM-164 and gemcitabine alone and in combination. Survival of PC cells was reduced as the dose of SM-164 increased. SM-164 and/or gemcitabine increased the number of apoptotic and dead PC cells, and expression of cleavage fragments of caspase-3 and PARP1, and inhibited tumor xenograft growth in nude mice. The inhibitory effect of combination treatment was greater and of longer duration than monotherapy. Neither combination nor monotherapy showed any significant toxicity in vivo. Apoptosis and necrosis, decreased expression of Ki67, and increased expression of cleaved caspase-3 were observed in xenograft tumor tissues in SM164/gemcitabine-treated mice. SM-164 could be a promising new agent for treatment of PC in combination with gemcitabine.