Open AccessInterferon‐alpha modulates the chemosensitivity of CD 133‐expressing pancreatic cancer cells to gemcitabine
Author(s) -
Hayashi Tomomi,
Ding Qiang,
Kuwahata Taisaku,
Maeda Koki,
Miyazaki Yumi,
Matsubara Shuichiro,
Obara Toru,
Natsugoe Shoji,
Takao Sonshin
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02235.x
Subject(s) - gemcitabine , pancreatic cancer , cancer research , apoptosis , cytotoxic t cell , cytokine , cancer cell , cell culture , interferon , cancer stem cell , carcinogenesis , chemistry , biology , cancer , medicine , immunology , in vitro , biochemistry , genetics
Pancreatic cancer is a lethal disease as current chemotherapies with gemcitabine ( GEM ) are still insufficient. Accumulating evidence suggests that cancer stem cells ( CSC ) are responsible for chemoresistance and that CD 133 is one of the CSC markers in pancreatic cancer. Interferon‐alpha ( IFN ‐α), a cytokine with pleiotropic effects, has direct cytotoxic and cytostatic effects on tumor cells. The aim of the present study was to investigate whether IFN ‐α can modulate the chemosensitivity of a human pancreatic cancer cell line, Capan‐1, to GEM . Cell cycles were evaluated for response to GEM with and without IFN ‐α by B rd U assay. GEM inhibited Capan‐1 cell growth in a dose‐dependent manner. GEM ( IC 50 ; 100 ng/ mL ) treatment reduced the number of both CD 133 + and CD 133 − cells in the S phase, induced apoptosis of CD 133 − cells more than that of CD 133 + cells and increased accumulation of CD 133 + cells into the G 0/ G 1 phase. These results infer that CD 133 + cells take shelter into the G 0/ G 1 phase from GEM treatment. IFN ‐α modulated CD 133 + cells from the G 0/ G 1 phase to the S phase. Consequently, apoptosis was accelerated in both CD 133 + and CD 133 − cells after IFN ‐α combined with GEM treatment. Furthermore, GEM combined with IFN ‐α treatment showed a significant tumor suppressive effect in the in vivo study. Importantly, CD 133 + cells showed CSC ‐like properties, such as generation of spheres, highly invasive ability and high tumorigenesis. These results suggest that IFN ‐α, as a modulator, could contribute to the treatment of CD 133 + cancer cells and be effective in combined chemotherapies with GEM for pancreatic cancer stem‐like cells. ( Cancer Sci 2012; 103: 889–896)