Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells

Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed K. Hassanein, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman

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Abstract

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 IC50 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). IC50 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 of 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.

Original languageEnglish
Pages (from-to)2774-2780
Number of pages7
JournalCell Cycle
Volume12
Issue number17
DOIs
Publication statusPublished - Sep 1 2013

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Keywords

  • Amino acid auxotrophy
  • Chemoresistance
  • Confocal microscopy
  • Fluorescence imaging
  • GFP
  • Pancreatic cancer
  • RFP
  • Salmonella typhimurium
  • Selective tumor targeting
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Hiroshima, Y., Zhao, M., Zhang, Y., Maawy, A., Hassanein, M. K., Uehara, F., Miwa, S., Yano, S., Momiyama, M., Suetsugu, A., Chishima, T., Tanaka, K., Bouvet, M., Endo, I., & Hoffman, R. M. (2013). Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells. Cell Cycle, 12(17), 2774-2780. https://doi.org/10.4161/cc.25872