Guilu Erxian Glue () Inhibits Chemotherapy-Induced Bone Marrow Hematopoietic Stem Cell Senescence in Mice May via p16INK4a-Rb Signaling Pathway.

Abstract

OBJECTIVE:

To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism.

METHODS:

The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX (100 mg/kg i.p.) was administrated to mice from day 1 to day 3 (d1-d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α (2.2 mg/(kg·d) i.p.) for 6 consecutive days (d4-d9), GEG (9.5 g/(kg·d) i.p.) for 9 consecutive days (d1-d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and β -galactosidase (β -gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2 (CDK2), CDK4, inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16 (p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma (pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively.

RESULTS:

Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced β -gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group (P<0.05 or P<0.01).

CONCLUSION:

GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.

• Authors: Jue Wang, Yin-Yin Ying, Zhao-Hui Chen, Ke-Ding Shao, Wei-Ping Zhang, Sheng-You Lin
• Journal: Chinese journal of integrative medicine (Chin J Integr Med) Vol. 26 Issue 11 Pg. 819-824 (Nov 2020) ISSN: 1672-0415 [Print] China
• PMID: 32915425 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• Cyclin-Dependent Kinase Inhibitor p16
• Drugs, Chinese Herbal
• Cyclophosphamide

Topics

• Animals
• Antineoplastic Agents, Alkylating (adverse effects)
• Bone Marrow (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cellular Senescence (drug effects)
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Cyclophosphamide (adverse effects)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Hematopoietic Stem Cells (drug effects)
• Male
• Mice