ABSTRACT
OBJECTIVE: To investigate the antitumour efficacy of luteolin on gastric cancer (GC) and study the mechanism underpinning the action. METHODS: Effects of luteolin on cell growth inhibition, apoptosis, and cell cycle arrest in MKN45 cells were investigated using the cell counting kit-8 assay. Changes in the mitochondrial membrane potential after luteolin treatment were assessed using 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanineiodi-de (JC-1) staining. To investigate whether apoptotic effect by luteolin is related to the phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) pathway, cells were additionally treated with LY294002, a PI3K/Akt pathway inhibitor. Moreover, the expressions of apoptosis-related proteins, namely B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein (Bax), Akt, p-Akt, caspase-3, and cytochrome C, were detected after luteolin treatment. RESULTS: The study revealed that in MKN45 cells, luteolin could inhibit the cell proliferation in a time- and dose-dependent manner; block the cell cycle in the S-phase; induce apoptosis; reduce the mitochondrial membrane potential; increase the expression of Bax, caspase-3, and cytochrome C; and decrease the expression of Bcl-2 and p-Akt. Luteolin might be involved in the PI3K/Akt signalling pathway, indicating that this pathway could be a therapeutic target for GC treatment. CONCLUSION: Luteolin could inhibit the proliferation of GC cells and block the cell cycle in the S-phase. The mechanism of inducing apoptosis in these cells was related to the PI3K/Akt signalling pathway.
Subject(s)
Proto-Oncogene Proteins c-akt , Stomach Neoplasms , Humans , Apoptosis , bcl-2-Associated X Protein/metabolism , Caspase 3 , Cell Line, Tumor , Cell Proliferation , Cytochromes c , Luteolin/pharmacology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2 , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolismABSTRACT
The multidisciplinary synthetic therapy for the colorectal liver metastases has been a hot spot in clinical research,which includes operative therapy,tumor local therapy,conversion therapy,chemotherapy, molecular targeted therapy and so on. It is need to choose multiple therapies for the patients and make the whole treatment strategy in accordance with the condition of patients to maximize the survival benefit in clinical prac-tice. So,it is important to comprehend the newest research process of the clinical therapy to make a good choice for the colorectal liver metastases patients.
ABSTRACT
Advanced gastric cancer has a low survival rate while traditional Chinese medicine (TCM) therapy has effects in inhibiting tumor growth, lengthening survival time and improving the quality of life.
