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Tumor-associated macrophages attenuate apoptosis-inducing effect of sorafenib in hepatoma cells by increasing autophagy / 南方医科大学学报
Journal of Southern Medical University ; (12): 264-270, 2019.
Article in Chinese | WPRIM | ID: wpr-772070
ABSTRACT
OBJECTIVE@#To explore the molecular mechanism of sorafenib resistance in hepatoma cells and identify for new targets to reverse drug resistance.@*METHODS@#THP-1 cells were induced into M2 tumor-associated macrophages (M2-TAMs) in vitro and identified by immunofluorescence. SMMC-7721 cells were co-cultured with M2-TAMs with or without sorafenib treatment. CCK-8 assay was used to observe the inhibitory effect of sorafenib on the cell proliferation. Annexin V/PI double staining and protein immunoblotting were used to assess the effect of sorafenib on the proliferation, apoptosis and the expressions of apoptosis-related proteins and autophagy-related protein in SMMC-7721 cells co-cultured with M2-TAMs in the presence or absence of the autophagy inhibitor chloroquine (CQ).@*RESULTS@#The IC of sorafenib at 48 h was 2.25 μmol/L in SMMC-7721 cells cultured alone, and increased to 4.72 μmol/L in the cells co-cultured with M2-TAMs. Compared with the cells cultured alone, the co-cultured SMMC-7721 cells showed significantly reduced apoptosis rate in response to sorafenib ( < 0.01) and significantly increased expression of Bcl-2 and Bcl-2/Bax ratio ( < 0.05) with also increased LC3-II/LC3-I ratio ( < 0.001) and lowered expression of p62 ( < 0.05), suggesting a significantly enhanced level of autophagy. CQ treatment significantly inhibited the proliferation of the co-cultured SMMC-7721 cells ( < 0.05), increased the cell apoptosis ( < 0.05) and reduced the Bcl-2/Bax ratio ( < 0.01).@*CONCLUSIONS@#M2-TAMs can attenuate the inhibitory effect of sorafenib on the proliferation of hepatoma cells by increasing the level of autophagy, suggesting a new strategy for reversing sorafenib resistance induced by the tumor microenvironment by inhibiting autophagy.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Autophagy / Apoptosis / Carcinoma, Hepatocellular / Cell Line, Tumor / Sorafenib / Liver Neoplasms / Macrophages Limits: Humans Language: Chinese Journal: Journal of Southern Medical University Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Autophagy / Apoptosis / Carcinoma, Hepatocellular / Cell Line, Tumor / Sorafenib / Liver Neoplasms / Macrophages Limits: Humans Language: Chinese Journal: Journal of Southern Medical University Year: 2019 Type: Article