和田, 佑馬 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
徳田, 和憲 Tokushima University
森根, 裕二 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
沖川, 昌平 Tokushima University
山下, 祥子 Tokushima University KAKEN研究者をさがす
池本, 哲也 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
居村, 暁 Tokushima University KAKEN研究者をさがす
齋藤, 裕 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
山田, 眞一郎 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
島田, 光生 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Introduction: The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation.
Materials and Methods: The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 μg/ml). Activated HSCs (aHSCs) were detected by α-SMA and IL-6 mRNA expressions and cytokine arrays of HSC’s culture supernatants. Cancer cell growth was analyzed for proliferation and migration ability, compared with TU-100 treatment. To investigate the direct anti-tumor effect of TU-100, cancer cells were cultured in the presence of aHSC-CM and TU-100 (90, 270, 900) or aHSC-CM alone, and assessed autophagosomes, conversion to LC3-II protein, and Beclin-1 mRNA expression.
Results: Colon cancer-CM significantly increased α-SMA and IL-6 mRNA expressions of aHSC. α-SMA and IL-6 mRNA expressions of aHSC, and IL-6 secretions from aHSCs were significantly decreased with TU-100 (270, 900) treatment, compared to colon cancer-CM alone. Compared with normal culture medium, aHSC-CM led to a significantly increased cell number and modified HSC-CM (TU-100; 270, 900) significantly suppressed cancer cell growth and migration. TU-100 (900) treatment induced autophagy and significantly promoted the autophagic cell death.
Conclusions: TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells.
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