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AIM: To study the inhibitory effect and mechanism of Jolkinolide B (JB) on the proliferation and metastasis of colon cancer HT-29 cells. METHODS: HT-29 cells were treated with different concentrations of JB, the cell proliferation rate was detected by MTT method, the cell clone formation rate was detected by plate cloning experiment, the cell cycle change was detected by flow cytometry, the cell migration ability was analyzed by wound healing assay, the cell invasion ability was studied by Transwell assay, E-cadherin, N-cadherin, vimentin, Snail1, Snail2, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression levels were detected by immunofluorescence and Western blotting, and p-PI3K, PI3K, p-Akt, Akt, NF-κB P65and p-NF-κB P65 protein expression levels were detected by Western blotting. HT-29 cells were treated with 100 μg/L IGF-1 and 100 μg/L IGF-1+20 μmol/L JB, respectively. The expression of PI3K/Akt/NF-κB pathway related proteins was detected by Western blotting. RESULTS: JB inhibited the proliferation of HT-29 cells in a concentration-dependent manner, with an IC
ABSTRACT
OBJECTIVE： To analyze the metabolites of jolkinolide B in rats， and predict its metabolism pathway. METHODS： The rats were randomly divided into blank group （0.5％ CMC-Na， ig） and administration group （jolkinolide B， ig， 100 mg/kg）， with 8 rats in each group. The fecal samples were collected at ＞0-12， ＞12-24， ＞24-36 hours after administration； the urine samples were collected at ＞0-2， ＞2-8， ＞8-12， ＞12-24， ＞24-36， ＞36-48 hours after administration； the blood samples were collected at 1， 2， 8， 12， 24， 36 hours after administration. UPLC-Q-TOF/MS combined with Analyst® TF 1.7.1 and PeakView® 2.2 software were used to analyze and identify the metabolites in the samples after treated with ultrasonic extraction， solid phase extraction and protein precipitation. RESULTS & CONCLUSIONS： Prototype drugs and seven metabolites were detected in rat’s fecal samples， and one or two metabolites were detected in urine and blood samples， respectively. After intragastric administration， the metabolism of jolkinolide B in rats is mainly through ring opening， oxidation， dehydration， deoxygenation and hydrogenation of phase Ⅰ， but no phase Ⅱ metabolites were detected.