CD133 expression in pancreatic cancer correlates with poor prognosis and increased metastasis. CD133⁺ pancreatic cancer cells exhibit cancer stem cell (CSC)-like properties. We established a CD133⁺ cell-rich subline from Capan-1 pancreatic cancer cells as a pancreatic CSC model and compared the effects of KU-0063794, a dual mTORC1/mTORC2 inhibitor, against those of mTORC1-specific rapamycin. We found that KU-0063794 prevents sphere formation, a self-renewal index, at high concentrations. Rapamycin inhibited sphere formation but to a lesser degree. In the present study, we aimed to determine the mechanistic roles of mTOR complex 2 (mTORC2) in maintaining CSC-like properties. By examining the PI3K/Akt/mTOR signaling pathway, we observed lower Akt phosphorylation in KU-0063794-treated cells. Phosphorylation of mTORC1 downstream effectors was inhibited by both inhibitors. Thus, mTORC2 activates Akt and modulate stem-like properties, whereas mTORC1 downstream signaling correlates directly with stem-like properties.

胰腺癌中CD133的表达与预后不良和转移增加有关。CD133 ⁺胰腺癌细胞表现出类似于癌症干细胞（CSC）的特性。我们建立了CD133 ⁺将来自Capan-1胰腺癌细胞的富含细胞的亚系作为胰腺CSC模型，并将KU-0063794（双重mTORC1 / mTORC2抑制剂）与mTORC1特异性雷帕霉素的作用进行了比较。我们发现，KU-0063794在高浓度下可防止球体形成（自我更新指数）。雷帕霉素抑制球的形成，但程度较小。在本研究中，我们旨在确定mTOR复合物2（mTORC2）在维持类CSC特性方面的机械作用。通过检查PI3K / Akt / mTOR信号通路，我们在KU-0063794处理的细胞中观察到了较低的Akt磷酸化。两种抑制剂均抑制mTORC1下游效应子的磷酸化。因此，mTORC2激活Akt并调节茎样特性，而mTORC1下游信号直接与茎样特性相关。