Chaihu Guizhi Decoction plus or minus formula combined with capecitabine inhibits IL-6/STAT3 signaling to suppress triple-negative breast cancer xenografts in nude mice.
10.12122/j.issn.1673-4254.2022.06.15
- Author:
Yu Xiao FANG
1
;
Shu Mei WANG
1
;
Qian YANG
1
;
Song Fan YOU
1
;
Xiang Ling XING
1
Author Information
1. Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
- Publication Type:Journal Article
- Keywords:
Chaihu Guizhi decoction;
IL-6/STAT3 signaling pathway;
apoptosis;
triple-negative breast cancer
- MeSH:
Animals;
Capecitabine/pharmacology*;
Cyclin D1/metabolism*;
Drugs, Chinese Herbal;
Heterografts;
Humans;
Interleukin-6/metabolism*;
Mice;
Mice, Nude;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
RNA, Messenger/metabolism*;
STAT3 Transcription Factor/metabolism*;
Signal Transduction;
Triple Negative Breast Neoplasms/drug therapy*;
bcl-2-Associated X Protein/metabolism*
- From:
Journal of Southern Medical University
2022;42(6):905-912
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of Chaihu Guizhi Decoction (CHGZD) combined with capecitabine on growth and apoptosis of subcutaneous triple-negative breast cancer xenografts in nude mice and explore the possible mechanism.
METHODS:Nude mouse models bearing subcutaneous triple-negative breast cancer xenografts were randomized into 6 groups (n=10) for treatment with distilled water (model group), low (10.62 g/kg), medium (21.23 g/kg) and high (42.46 g/kg) doses of CHGZD, capecitabine (0.2 mg/kg), or the combination of CHGZD (42.46 g/kg) and capecitabine (0.2 mg/k) once daily for 21 consecutive days. The general condition of mice was observed, and after 21-day treatments, the tumors were dissected for measurement of tumor volume and weight and histopathological examination with HE staining. Serum IL-6 levels of the mice were determined with enzyme-linked immunosorbent assay (ELISA), and the expression levels of IL-6, STAT3, p-STAT3, Bax, Bcl-2 and cyclin D1 in the tumor tissues were detected using real-time PCR and Western blotting.
RESULTS:Compared with those in the model group, the tumor-bearing mice receiving treatments with CHGZD showed significantly increased food intake with good general condition, sensitive responses, increased body weight, and lower tumor mass (P < 0.01). Compared with capecitabine treatment alone, treatment with CHGZD alone at the medium and high doses and the combined treatment all resulted in significantly higher tumor inhibition rates (P < 0.01), induced obvious tumor tissue degeneration and reduced the tumor cell density. Treatments with CHGZD, both alone and in combination with capecitabine, significantly decreased serum IL-6 level, lowered the mRNA expression levels of IL-6 and STAT3, the protein expressions of IL-6, STAT3 and P-STAT3 (P < 0.05), and the mRNA and protein expressions of Bcl-2 and cyclin D1 (P < 0.05), and increased the mRNA and protein expressions of Bax in the tumor tissues (P < 0.05).
CONCLUSION:CHGZD combined with capecitabine can significantly inhibit tumor growth in nude mice bearing triple-negative breast cancer xenografts, the mechanism of which may involve the inhibition of IL-6/STAT3 signaling pathway and regulation of Bax, Bcl-2 and cyclin D1 expressions to suppress tumor cell proliferation and differentiation and induce cell apoptosis.
