title: Secreted protein acidic and rich in cysteine enhances the chemosensitivity of pancreatic cancer cells to gemcitabine.
abstract: It has been previously shown that the simultaneous exposure of colon cancer cells MIP to irinotecan and secreted protein acidic and rich in cysteine (SPARC) enhances anticancer activity. However, whether there is same effect of SPARC in pancreatic cancer remains largely unknown. Therefore in this study, we aimed to investigate the role of SPARC played in the sensitivity of pancreatic cancer to gemcitabine. We first treated MIAPaCa2 and MIAPaCa2/SPARC69 cells with different concentrations of gemcitabine (2, 5, 10, and 20 μM) for 24, 48, and 72 h and selected the appropriated concentration for further study. Then we analyzed cell viability, cell cycle, and apoptosis and the levels of apoptosis-related proteins by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting and Western blot were used, respectively. In this study, we found that gemcitabine inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Overexpression of SPARC increased the inhibiting effect of gemcitabine on pancreatic cancer cells. The colony size of MIAPaCa2/SPARC69 was much smaller than that of MIAPaCa2/V. There was a G0/G1 arrest with significant increase of apoptosis after gemcitabine treatment in MIAPaCa2/SPARC69 cells. Furthermore, our results demonstrated that overexpression of SPARC markedly increased the levels of pro-apoptotic proteins in gemcitabine-treated pancreatic cancer cells. The SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins. These results have shown that the SPARC/ gemcitabine combination treatment may be a potentially useful therapeutic option for individuals diagnosed with pancreatic cancer.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China.
authors.forename: Zhengfa
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Gynecology and Obstetrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Senior officer's Health Care, Nanjing General Hospital of Nanjing Military Area Command, Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China.
authors.forename: ShengChun
authors.initials: S
authors.lastname: Dang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China.
authors.forename: Xuqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu Province, 212001, People's Republic of China. jxzhang57@hotmail.com.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D015676:Osteonectin / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D015676:Osteonectin; C577241:SPARC protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Chemosensitivity; Gemcitabine; Pancreatic cancer; SPARC