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Guilu Erxian Glue (龟鹿二仙胶) Inhibits Chemotherapy-Induced Bone Marrow Hematopoietic Stem Cell Senescence in Mice May via p16INK4a-Rb Signaling Pathway.
- Source :
- Chinese Journal of Integrative Medicine; 2020, Vol. 26 Issue 11, p819-824, 6p
- Publication Year :
- 2020
-
Abstract
- Objective: To evaluate the effect of Guilu Erxian Glue (龟鹿二仙胶, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism. Methods: The H<subscript>22</subscript> liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 10<superscript>6</superscript>/mL H<subscript>22</subscript> 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 (p16<superscript>INK4a</superscript>), p21<superscript>Cip1/Waf1</superscript>, 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 p16<superscript>INK4a</superscript>, p53 and p21<superscript>Cip1/Waf1</superscript> 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 p16<superscript>INK4a</superscript>-Rb signaling pathway might be the underlying mechanism. [ABSTRACT FROM AUTHOR]
- Subjects :
- AGING
ANIMAL experimentation
BIOLOGICAL models
BONE marrow
CANCER chemotherapy
CELL physiology
CELLULAR signal transduction
GENE expression
HEMATOPOIETIC stem cells
HERBAL medicine
CHINESE medicine
MICE
POLYMERASE chain reaction
PROTEINS
TRANSFERASES
WESTERN immunoblotting
REVERSE transcriptase polymerase chain reaction
CYCLOPHOSPHAMIDE
MICRORNA
DRUG administration
DRUG dosage
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 16720415
- Volume :
- 26
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Chinese Journal of Integrative Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 147156159
- Full Text :
- https://doi.org/10.1007/s11655-020-3098-3