Synergistic antitumor interactions between gemcitabine and clofarabine             in human pancreatic cancer cell lines.
Pancreatic cancer is a highly malignant disease, with a 5-year survival             rate of less than 4%. Thus, new therapies for this deadly disease are urgently             required. In this study, we sought to investigate whether combination treatments             with gemcitabine and clofarabine result in synergistic cytotoxic effects against             human pancreatic cancer cells. The type and extent of cytotoxic interactions between             gemcitabine and clofarabine in three human pancreatic cancer cell lines were determined             by MTT assays and standard isobologram analysis. The effects of the two agents             on cell cycle distribution and apoptosis were determined by flow cytometry. Clofarabine             significantly and synergistically enhanced gemcitabine cytotoxicities in all of             the cell lines tested. This was accompanied by a nearly complete S phase arrest             and synergistic induction of apoptosis (cooperativity index = 0.67). Combined             treatment of gemcitabine and clofarabine resulted in synergistic cytotoxicities             in vitro. Our results strongly suggest potential clinical benefits for using this             drug combination to treat pancreatic cancer patients.
The State Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun, PR China.
Yingjie
Y
Guo
Xuelian
X
Xu
Wenxiu
W
Qi
Chengzhi
C
Xie
Guan
G
Wang
Aijun
A
Zhang
Yubin
Y
Ge
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001087:Arabinonucleosides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000077866:Clofarabine; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D000093542:Gemcitabine
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D003841:Deoxycytidine; D000077866:Clofarabine; D000093542:Gemcitabine