title: Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.
abstract: Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis among all malignancies and is resistant to almost all current therapies. Attenuated Salmonella typhimurium strain VNP20009 has been deployed as powerful anticancer agent in a variety of animal cancer models, and previous phase 1 clinical trials have proven its safety profiles. However, thus far, little is known about its effect on PDAC. Here, we established CFPAC-1 cell lines expressing an mKate2 protein and thus emitting far-red fluorescence in the subsequent xenograft implant. VNP20009 strain was further engineered to carry a luciferase cDNA, which catalyzes the light-emitting reaction to allow the observation of salmonella distribution and accumulation within tumor with live imaging. Using such VNP20009 strain and intratumoral delivery, we could reduce the growth of pancreatic cancer by inducing apoptosis and severe necrosis in a dosage dependent manner. Consistent with this finding, intratumoral delivery of VNP20009 also increase caspase-3 activity and the expression of Bax protein. In summary, we revealed that VNP20009 is a promising bacterial agent for the treatment of PDAC, and that we have established a dual fluorescent imaging system as a valuable tool for noninvasive live imaging of solid tumor and engineered bacterial drug.
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Sujin
authors.initials: S
authors.lastname: Zhou
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Gong
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Li
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Pan
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.affiliation: b Department of Clinical Laboratory , The Fourth Affiliated Hospital of Harbin Medical University , Harbin , Heilongjiang , China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Gao
authors.affiliation: a Collaborative Innovation Center for Cancer Medicine, The Center of Metabolic Disease Research, Nanjing Medical University , Nanjing , Jiangsu Province , China.
authors.forename: Allan Z
authors.initials: AZ
authors.lastname: Zhao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D012486:Salmonella typhimurium / Q000378:metabolism*
keywords: Attenuated Salmonella typhimurium; VNP20009; bacteria therapy; far-red fluorescence; imaging; intratumoral delivery; pancreatic ductal adenocarcinoma