Downregulation of miR‑183 inhibits the growth of PANC‑1 pancreatic cancer cells in vitro and in vivo, and increases chemosensitivity to 5‑fluorouracil and gemcitabine

Yang,Xiaoping; Wang,Wei; Zhang,Xiong; Zou,Qi; Cai,Lei; Yu,Bo

doi:10.3892/etm.2018.7112

Downregulation of miR‑183 inhibits the growth of PANC‑1 pancreatic cancer cells in vitro and in vivo, and increases chemosensitivity to 5‑fluorouracil and gemcitabine

Authors:
- Xiaoping Yang
- Wei Wang
- Xiong Zhang
- Qi Zou
- Lei Cai
- Bo Yu
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Affiliations: Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China
Published online on: December 19, 2018 https://doi.org/10.3892/etm.2018.7112
Pages: 1697-1705
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer (PC) is a common malignancy with a poorly understood pathogenesis. Currently, the efficacy of anti‑PC therapies is insufficient, partially due to the chemoresistance of cancer cells. The present study aimed to elucidate the role of miR‑183 in the proliferation, apoptosis, and chemosensitivity to 5‑fluorouracil and gemcitabine of human PC cells and the associated mechanisms. PANC‑1 cells were transfected with microRNA (miR)‑183 inhibitors, and the effect of miR‑183 on cell proliferation was evaluated via MTT assay. Apoptosis and cell cycle distribution were determined by flow cytometry. In vivo tumor xenograft models of PANC‑1 cells were generated in BALB/c nude mice to examine the effect of miR‑183 downregulation on tumor growth. Furthermore, components of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway were examined via reverse transcription‑quantitative polymerase chain reaction and western blotting in the collected cells. Finally, PANC‑1 cells were treated with 5‑fluorouracil or gemcitabine and transfected with miR‑183 inhibitors, and the viability of cells was determined by MTT assay. The results demonstrated that knockdown of miR‑183 could significantly decrease proliferation and promote apoptosis of PANC‑1 cells. The cells transfected with miR‑183 inhibitors were significantly arrested at the G1 phase (P<0.01). Furthermore, miR‑183 downregulation led to significant decreases in the mRNA levels of PI3K, Akt and B cell lymphoma‑2 (Bcl‑2) expression (P<0.001), and significant increases in PTEN and Bcl‑2 associated X protein expression in PANC‑1 cells (P<0.001). Knockdown of miR‑183 was able to significantly increase the chemosensitivity of PANC‑1 cells to 5‑fluorouracil and gemcitabine. These results indicate that downregulation of miR‑183 can inhibit the growth of PC cells in vitro and in vivo, and increase cell sensitivity to 5‑fluorouracil and gemcitabine through regulating the PTEN/PI3K/Akt signaling pathway.

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