Therapy of Smac mimetic SM-164 in combination with gemcitabine for pancreatic cancer |
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| Authors: | Bin Zhou Jie Zhang Ge Chen Lei You Tai-Ping Zhang Yu-Pei Zhao |
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| Affiliation: | 1. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China;2. Department of Hepatobiliary Surgery, The Affiliated Hospital of Medical College, Qingdao University, Shandong Province, China;3. National Laboratory of Medical Molecular Biology, Beijing, China |
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| Abstract: | 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. |
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| Keywords: | Pancreatic cancer SM-164 Gemcitabine Combination therapy Apoptosis |
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