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.

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.