PMID- 32648126 OWN - NLM STAT- MEDLINE DCOM- 20220526 LR - 20220526 IS - 1993-0402 (Electronic) IS - 1672-0415 (Linking) VI - 28 IP - 6 DP - 2022 Jun TI - Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway. PG - 524-530 LID - 10.1007/s11655-020-3265-6 [doi] AB - 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 G(1) phase arrest in gastric cancer cells. CI - (c) 2020. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Zheng, Chun-Lei AU - Zheng CL AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Hou, Ke-Zuo AU - Hou KZ AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Wang, An-Qi AU - Wang AQ AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Fang, Wan-Xia AU - Fang WX AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Yu, Shi-Tong AU - Yu ST AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Liang, Jin-E AU - Liang JE AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Qi, Hai-Yan AU - Qi HY AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Qu, Xiu-Juan AU - Qu XJ AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Liu, Yun-Peng AU - Liu YP AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. FAU - Che, Xiao-Fang AU - Che XF AD - Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China. xfche@cmu.edu.cn. AD - Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. xfche@cmu.edu.cn. AD - Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, China. xfche@cmu.edu.cn. LA - eng PT - Journal Article DEP - 20200709 PL - China TA - Chin J Integr Med JT - Chinese journal of integrative medicine JID - 101181180 RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Apoptosis MH - Cell Line, Tumor MH - Cell Proliferation MH - Cyclin D1/genetics/metabolism/pharmacology MH - Humans MH - *Interleukin-6/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - STAT3 Transcription Factor/metabolism MH - *Stomach Neoplasms/drug therapy/genetics OTO - NOTNLM OT - Chinese herbal medicine OT - G1 arrest OT - Kang-Ai Injection OT - gastric cancer OT - interleukin-6 OT - signal transducer and activator of transcription 3 EDAT- 2020/07/11 06:00 MHDA- 2022/05/27 06:00 CRDT- 2020/07/11 06:00 PHST- 2019/12/26 00:00 [accepted] PHST- 2020/07/11 06:00 [pubmed] PHST- 2022/05/27 06:00 [medline] PHST- 2020/07/11 06:00 [entrez] AID - 10.1007/s11655-020-3265-6 [pii] AID - 10.1007/s11655-020-3265-6 [doi] PST - ppublish SO - Chin J Integr Med. 2022 Jun;28(6):524-530. doi: 10.1007/s11655-020-3265-6. Epub 2020 Jul 9.