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Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway

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Abstract

Objective

To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.

Methods

Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.

Results

KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01).

Conclusion

KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.

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Authors and Affiliations

  1. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China

    Chun-lei Zheng, Ke-zuo Hou, An-qi Wang, Wan-xia Fang, Shi-tong Yu, Jin-e Liang, Hai-yan Qi, Xiu-juan Qu, Yun-peng Liu & Xiao-fang Che

  2. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China

    Chun-lei Zheng, Ke-zuo Hou, An-qi Wang, Wan-xia Fang, Shi-tong Yu, Jin-e Liang, Hai-yan Qi, Xiu-juan Qu, Yun-peng Liu & Xiao-fang Che

  3. Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China

    Chun-lei Zheng, Ke-zuo Hou, An-qi Wang, Wan-xia Fang, Shi-tong Yu, Jin-e Liang, Hai-yan Qi, Xiu-juan Qu, Yun-peng Liu & Xiao-fang Che

Authors
  1. Chun-lei Zheng
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  2. Ke-zuo Hou
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  10. Xiao-fang Che
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Contributions

Che XF and Liu YP designed the study. Zheng CL and Hou KZ performed the experiments and drafted the manuscript. Wang AQ, Fang WX, Yu ST, Liang JE and Qi HY performed a portion of the experiments. Che XF, Liu YP and Qu XJ revised the manuscript. All authors read and approved the final manuscript for publication.

Corresponding author

Correspondence to Xiao-fang Che.

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Conflict of Interest

The authors declare no financial or commercial conflict of interest.

Supported by National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2017ZX09304025), Construction Program of Clinical Cooperation Ability of Chinese and Western Medicine for Major and Difficult Diseases (No. 2019-163), the Key Research and Development Program of Liaoning Province (No. 2018225060), Science and Technology Plan Project of Liaoning Province (No. 2016007010), and Science and Technology Plan Project of Shenyang City (No. 19-112-4-099)

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Zheng, Cl., Hou, Kz., Wang, Aq. et al. Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway. Chin. J. Integr. Med. 28, 524–530 (2022). https://doi.org/10.1007/s11655-020-3265-6

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  • DOI: https://doi.org/10.1007/s11655-020-3265-6

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