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| Xihuang Pill (西黄丸) Induces Mesenchymal-Epithelial Transition and Inhibits Loss of Apical-Basal Polarity in Colorectal Cancer Cell through Regulating ZEB1-SCRIB Loop |
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| KeyWord:Xihuang Pill, anti-metastasis, epithelial-mesenchymal transition, apical-basal polarity, colorectal cancer |
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| Abstract: |
| Objective: To investigate the antiproliferative and anti-metastasis effect of Xihuang Pill (西黄丸, XP) on human colorectal cancer cell and to explore the molecular mechanism by which it produces the effects. Methods: Highly metastatic human colorectal cancer cell line LoVo was treated with low-, medium-, and high- dose XP-containing serum (XP-L, XP-M, XP-H) groups for 48 h, cells intervened with no drug rat serum and PD98059 [extracellular signal-regulated kinase (ERK) inhibitor] as negative and positive controls (NC and PC) groups. Cell proliferation assay was made using cell counting kit-8 (CCK8). The 8 μm pore-size transwell chamber and 4', 6-diamidino-2-phenylindole (DAPI) staining were applied to examine the ability of invasion and migration of the cells. The protein expression of ERK1/2, zinc finger E-box-binding homeobox 1 (ZEB1), Scrib and lethal giant larvae homolog 2 (Lgl2) was detected by Western blotting while the relative mRNA quantity of E-cadherin, N-cadherin, Occludin and junctional adhesion molecule-1 (JAM1) was measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Results: XP induced a dose-dependent suppression on the proliferation of LoVo cells (P<0.05 or P<0.01), with the inhibition rates varied from 27.30% to 31.08%. Transwell assay showed that when preprocessed with PD98059 and XP-containing serum, the number of cells that passed the filter decreased significantly compared with that of NC group (P<0.05 or P<0.01). Moreover, XP inhibited the protein expression of ERK1/2 and ZEB1 (P<0.05); and up-regulated the protein expression of Scrib and Lgl2 (P<0.05). The mRNA levels of E-cadherin, Occludin and JAM1 of the XP intervened groups and PC group markedly ascended (P<0.05) while that of N-cadherin showed a descending tendency (P>0.05). Conclusion: XP intervention suppressed the ability of proliferation, invasion and migration of the LoVo cells. Regulating ZEB1-SCRIB Loop so as to recover epithelial phenotype and apical junctional complex might be one of the mechanisms by which XP produces the anti-metastasis effect. |
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