Romanian Society of Pharmaceutical Sciences

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MECHANISM OF CELASTRUS ORBICULATUS EXTRACT INHIBITING THE INVASION AND METASTASIS OF GASTRIC CANCER CELLS THROUGH RAC1/LIMK1/COFILIN 1 PATHWAY

RUI HUANG 1, XIN SONG 2, AIDONG CHEN 3, HAO JIANG 4*

1 Department of Academic Theory Research, Mudanjiang Medical University, Mudanjiang, 157011, Heilongjiang, China
2 Department of Pathology, Mudanjiang Tumour Hospital, Mudanjiang, 157011, Heilongjiang, China
3 Department of Gastroenterology, Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, 157011, Heilongjiang, China
4 Department of General Surgery, Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, 157011, Heilongjiang, China

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Celastrus orbiculatus extract contains various biologically active components which have extensive medicinal value. The present work investigated the inhibitory mechanism of Celastrus orbiculatus extract on the invasion and metastasis of gastric cancer (GC) cells (GCCs), with particular emphasis on the function of the ras-related C3 botulinum toxin substrate 1 (Rac1)/LIM domain kinase 1 (LIMK1)/cofilin1 signalling pathway (SPW) in this process. First, celastrin was extracted from Celastrus orbiculatus using an ultrasonic extraction (ULE) method and detected by high-performance liquid chromatography (HPLC). The human GCC line MGC-803 was then used in the study. The prepared Celastrus orbiculatus samples showed the same chromatographic peak as the celastrol standard. In contrast to the Ctrl group, the cell proliferation rates (CPRs) and cell invasion rates (CIRs) in groups A, B and C were greatly reduced, while the cell apoptosis rates (CARs) and cell migration rates (CMRs) were greatly increased (p < 0.05). In addition, the Rac1/LIMK1/cofilin1 SPW-associated proteins in the Celastrus orbiculatus treatment groups were strongly downshifted compared to the Ctrl group (p < 0.05). Meanwhile, there was a continuous downward trend with increased DC and time. Celastrus orbiculatus extract, by regulating the Rac1/LIMK1/cofilin1 SPW, suppressed proliferation, invasion and migration of GCCs while facilitating their apoptosis. This discovery provided important evidence for the potential use of Celastrus orbiculatus extract in treating GC.