著作: [和田 佑馬]/[徳田 和憲]/[森根 裕二]/[沖川 昌平]/[山下 祥子]/[池本 哲也]/[居村 暁]/[齋藤 裕]/[山田 眞一郎]/[島田 光生]/The inhibitory effect of TU-100 on hepatic stellate cell activation in the tumor microenvironment./[Oncotarget]
(英) The inhibitory effect of TU-100 on hepatic stellate cell activation in the tumor microenvironment.
(英) 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. The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 g/ml). Activated HSCs (aHSCs) were detected by -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. Colon cancer-CM significantly increased -SMA and IL-6 mRNA expressions of aHSC. -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. TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells.
|年月日||必須||2020年 12月 8日|