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Bioengineered miR‐1291prodrugas sensitizing agent for the control of pancreatic carcinoma cell proliferation and tumor growth
Author(s) -
Tu Meijuan,
Li Meimei,
Yu Aiming
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.935.12
Subject(s) - prodrug , abcc1 , cancer research , pancreatic cancer , medicine , microrna , chemotherapy , downregulation and upregulation , efflux , in vivo , doxorubicin , cell growth , pharmacology , transporter , cancer , chemistry , biology , atp binding cassette transporter , gene , biochemistry , microbiology and biotechnology
MicroRNAs (miRs or miRNAs) are critical factors in the control of tumor initiation and progression via crosstalk with cancer signaling pathways. Our recent studies have demonstrated that miR‐1291 is able to sensitize pancreatic carcinoma cells to chemotherapy through downregulation of efflux transporter ABCC1/MRP1. We have also developed a novel biological method to produce large quantity ofmiR‐1291 prodrug for research and development. In this study, we aimed to assess the utility of bioengineered miR‐1291 prodrug for improving the efficacy of chemotherapy. Our data showed that miR‐1291 prodrug was readily processed to mature miR‐1291 in human carcinoma PANC‐1 cells and consequently reduced the protein levels of miR‐1291 targeted genes including efflux transporter ABCC1/MRP1. Furthermore, miR‐1291 prodrug significantly enhanced the sensitivity of ABCC1‐overexpressing PANC‐1 cells to doxorubicin, a substrate of ABCC1. In addition, in vivo ‐jetPEI formulated miR‐1291 prodrug was distributed to PANC‐1 xenograft tumors in mouse models and enhanced the efficacy of chemotherapy. These results indicate that bioengineered miR‐1291prodrug may be utilized as sensitizing agent for the development of more effective cancer therapy. Support or Funding Information National Institutes of Health (1U01CA175315 to A.M.Y.)