首页|Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Objective:To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods:Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary glands.Sixty-six mice were randomly assigned into 6 groups(n=11 in ench):naïve,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naïve group,each mouse received subcutaneous inoculation with 5×105 4T1 cells resuspended in 100 μ L of normal saline in the mammary fat pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naïve mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results:Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P＜0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological activities.Moreover,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P＜0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response(P＜0.05).Conclusion:The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement.

adjunctive therapybreast cancercytokinesChinese medicinetumor microenvironment

Lea Ling-Yu Kan、Ben Chung-Lap Chan、Grace Gar-Lee Yue、LI Pei-ting、Sharon Sze-Man Hon、HUANG Dan-qi、Miranda Sin-Man Tsang、Clara Bik-San Lau、Ping-Chung Leung、Chun-Kwok Wong

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Institute of Chinese Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China

State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants,The Chinese University of Hong Kong,Hong Kong,China

Department of Chemical Pathology,The Chinese University of Hong Kong,Hong Kong SAR,China

China-Australia International Research Centre for Chinese Medicine,School of Health and Biomedical Sciences,STEM College,RMIT University,Bundoora,Victoria,Australia

Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine,The Chinese University of Hong Kong SAR,Hong Kong,China

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State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants(The Chinese University of HoChin R & D Centre for Chinese Medicine,CUHK,Hong KongC.C.Wu Cultural Foundation

2024

10.1007/s11655-023-3745-6

中国结合医学杂志(英文版)
中国中西医结合学会 中国中医研究院

中国结合医学杂志(英文版)

CSTPCD
影响因子：1.056
ISSN：1672-0415
年,卷(期)：2024.30(4)
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