Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
| Autor: | Ke-ping Shen, Xian Gu, Ling-yu Zhu, Zhen-ye Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Cyclophosphamide medicine.medical_treatment 03 medical and health sciences 0302 clinical medicine In vivo medicine Lung cancer RC254-282 Original Research myelosuppression HMGB1 Chemotherapy Chemistry astragaioside IV Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease saponins of rhizoma polygonati Haematopoiesis 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis 030220 oncology & carcinogenesis Cancer research mir-142-3p Bone marrow Stem cell medicine.drug |
| Zdroj: | Frontiers in Oncology, Vol 11 (2021) Frontiers in Oncology |
| DOI: | 10.3389/fonc.2021.630921/full |
| Popis: | Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs. |
| Databáze: | OpenAIRE |
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