Comparison of efficacy ofSalmonella typhimuriumA1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells

• DOI: 10.4161/cc.25872
• Publication Date: 2013-08-21T20:40:11Z
• Authors: Yukihiko Hiroshima; Ming Zhao; Yong Zhang; Ali Maawy; Mohamed Hassanein; Fuminari Uehara; Shinji Miwa; Shuya Yano; Masashi Momiyama; Atsushi Suetsugu; Takashi Chishima; Kuniya Tanaka; Michael Bouvet; Itaru Endo; Robert M. Hoffman
• Keywords: Salmonella typhimurium; 0301 basic medicine; Nude; pancreatic cancer; Drug Resistance; Mice, Nude; Antineoplastic Agents; GFP; confocal microscopy; Cell Line; Pancreatic Cancer; Mice; 03 medical and health sciences; Rare Diseases; amino acid auxotrophy; fluorescence imaging; Stem Cell Research - Nonembryonic - Human; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; RFP; Animals; Humans; Cancer; Microscopy; Tumor; Microscopy, Confocal; chemoresistance; Stem Cell Research; Xenograft Model Antitumor Assays; 3. Good health; stem cell; Pancreatic Neoplasms; Orphan Drug; selective tumor targeting; Treatment Outcome; Drug Resistance, Neoplasm; Confocal; Neoplastic Stem Cells; Neoplasm; Stem Cell Research - Nonembryonic - Non-Human; Biochemistry and Cell Biology; Digestive Diseases; Developmental Biology

The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like cells and round non-stem cells. We report here the in vitro IC 50 values of stem-like and non-stem XPA1 human pancreatic cells cells for: (1) 5-fluorouracil (5-FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting Salmonella typhimurium A1-R (A1-R). IC 50 values of stem-like XPA1 cells were significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and CDDP (P = 0.012). In contrast, there was no difference between the efficacy of A1-R on stem-like and non-stem XPA1 cells. In vivo, 5-FU and A1-R significantly reduced the tumor weight of non-stem XPA1 cells (5-FU; P = 0.028; A1-R; P = 0.011). In contrast, only A1-R significantly reduced tumor weight of stem-like XPA1 cells (P = 0.012). The combination A1-R with 5-FU improved the antitumor efficacy compared with 5-FU monotherapy on the stem-like cells (P = 0.004). The results of the present report indicate A1-R is a promising therapy for chemo-resistant pancreatic cancer stem-like cells.