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Tanshinone I induces apoptosis and pro-survival autophagy in gastric cancers.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2016 Jun; Vol. 77 (6), pp. 1171-81. Date of Electronic Publication: 2016 Apr 21. - Publication Year :
- 2016
-
Abstract
- Purpose: To investigate the occurrence of apoptosis and autophagy on human gastric cancer cells after treatment by Tanshinone I, as well as the relationship between them.<br />Methods: BGC823 and SGC7901 cells were treated with Tanshinone I; the cell proliferation was measured using CCK-8 and clone formation assay; and the expression of apoptosis- and autophagy-associated proteins was detected by Western blot. Autophagic vacuoles in cells were observed with LC3 dyeing using confocal fluorescent microscopy, and apoptotic cells were detected via flow cytometry. Bcl-2 was overexpressed in gastric cells treated with Tanshinone I or not, and autophagy relative protein was investigated; the interaction between Beclin-1 and Bcl-2 was detected by immunoprecipitation. Cell apoptosis was detected when autophagy was inhibited by ATG7-siRNA. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice.<br />Results: Tanshinone I inhibited the proliferation of BGC823 and SGC7901 cells, and induced cell apoptosis by inhibiting anti-apoptosis protein Bcl-2. Tanshinone I also increased the conversion of LC3I to LC3II and triggered autophagosome formation, without changing the expression of Beclin-1. However, the Beclin-1 VPS34 complexes were increased after Tanshinone I treatment via inhibiting Bcl-2 expression. Moreover, disturbing autophagy by knockdown of ATG7 expression contributed to Tanshinone I-induced apoptosis. In vivo assay showed that combination with autophagy inhibitor chloroquine in nude mice bearing BGC823 xenograft significantly augmented the antitumor effect of Tanshinone I.<br />Conclusions: Tanshinone I induced apoptosis and pro-survival autophagy via inhibiting Bcl-2 expression on gastric cancer, and the combination of chloroquine and Tanshinone I could inhibit tumor growth more efficiently than monotherapy, which might be considered as an effective strategy for the treatment for gastric cancer.
- Subjects :
- Abietanes administration & dosage
Animals
Antineoplastic Agents, Phytogenic administration & dosage
Beclin-1 metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Flow Cytometry
Humans
Mice, Inbred BALB C
Mice, Nude
Microscopy, Fluorescence
Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors
Stomach Neoplasms metabolism
Stomach Neoplasms pathology
Xenograft Model Antitumor Assays
Abietanes pharmacology
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Autophagy drug effects
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 77
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27100736
- Full Text :
- https://doi.org/10.1007/s00280-016-3034-6