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Tanshinone I induces apoptosis and pro-survival autophagy in gastric cancers

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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.

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.

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.

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.

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Acknowledgments

This work was supported by Shanghai Natural Science Foundation of China (13ZR1434300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University, 1400 West Beijing Road, Lane 24, Shanghai, Zip Code 200040, China

    Xiaoping Jing, Weiwei Cheng, Sheng Guo, Ya Zou & Li He

  2. Shanghai Biochip Co., Ltd, National Engineering Center for Biochip at Shanghai, Shanghai, 201203, China

    Yichun Xu

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  1. Xiaoping Jing
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Correspondence to Xiaoping Jing or Li He.

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Jing, X., Xu, Y., Cheng, W. et al. Tanshinone I induces apoptosis and pro-survival autophagy in gastric cancers. Cancer Chemother Pharmacol 77, 1171–1181 (2016). https://doi.org/10.1007/s00280-016-3034-6

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  • DOI: https://doi.org/10.1007/s00280-016-3034-6

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