Interferon-alpha modulates the chemosensitivity of CD133-expressing pancreatic cancer cells to gemcitabine
Interferon-alpha modulates the chemosensitivity of CD133-expressing pancreatic cancer cells to gemcitabine
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DOI：
10.1111/j.1349-7006.2012.02235.x
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发表时间：
2012-05-01
期刊：
影响因子：
5.7
通讯作者：
Takao, Sonshin
中科院分区：
文献类型：
--
作者：
Hayashi, Tomomi;Ding, Qiang;Takao, Sonshin
胰腺癌是一种致命的疾病，目前使用吉西他滨（GEM）的化疗仍然不足。越来越多的证据表明，癌症干细胞（CSC）负责化疗耐药，CD133是胰腺癌的CSC标志物之一。干扰素- α (IFN-a)是一种具有多效作用的细胞因子，对肿瘤细胞具有直接的细胞毒和细胞抑制作用。本研究的目的是研究IFN-a是否可以调节人类胰腺癌细胞系Capan-1对GEM的化学敏感性。通过BrdU法评估细胞周期对含IFN-a和不含IFN-a的GEM的反应。GEM抑制Capan-1细胞生长呈剂量依赖性。GEM （IC50； 100类似于ng/mL）处理可减少S期CD133+和CD133-细胞的数量，诱导CD133-细胞比CD133+细胞更多的凋亡，增加CD133+细胞进入G0/G1期的积累。这些结果推断CD133+细胞在GEM处理后进入G0/G1期。IFN-a调节CD133+细胞从G0/G1期进入S期。因此，IFN-a联合GEM处理后，CD133+和CD133-细胞的凋亡均加速。此外，GEM联合IFN-a治疗在体内研究中显示出显著的肿瘤抑制作用。重要的是，CD133+细胞表现出csc样特性，如球的生成、高侵袭能力和高致瘤性。这些结果表明，IFN-a作为一种调节剂，可以促进CD133+癌细胞的治疗，并且在联合化疗与GEM治疗胰腺癌干细胞样细胞中有效。（癌症科学2012；103:889896）
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 CD133 is one of the CSC markers in pancreatic cancer. Interferon-alpha (IFN-a), 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-a 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-a by BrdU assay. GEM inhibited Capan-1 cell growth in a dose-dependent manner. GEM (IC50; 100 similar to ng/mL) treatment reduced the number of both CD133+ and CD133- cells in the S phase, induced apoptosis of CD133- cells more than that of CD133+ cells and increased accumulation of CD133+ cells into the G0/G1 phase. These results infer that CD133+ cells take shelter into the G0/G1 phase from GEM treatment. IFN-a modulated CD133+ cells from the G0/G1 phase to the S phase. Consequently, apoptosis was accelerated in both CD133+ and CD133- cells after IFN-a combined with GEM treatment. Furthermore, GEM combined with IFN-a treatment showed a significant tumor suppressive effect in the in vivo study. Importantly, CD133+ cells showed CSC-like properties, such as generation of spheres, highly invasive ability and high tumorigenesis. These results suggest that IFN-a, as a modulator, could contribute to the treatment of CD133+ cancer cells and be effective in combined chemotherapies with GEM for pancreatic cancer stem-like cells. (Cancer Sci 2012; 103: 889896)