| He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironmentOA |
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| 作者姓名： | Jian-xiu Zhai Ze-hai Song Hang Chang Yu-wei Wang Na Han Zhi-hui Liu Jun Yin |
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| 作者单位： | Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China;Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110017, China;Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110018, China;Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110019, China;Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110020, China;Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110021, China;Key Laboratory of Northeast Plant Materials, Department of Pharmacognosy and Utilization, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110022, China |
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| 摘 要： | Objective:He-Wei Granule(HWKL) is a modern product derived from the modified formulation of traditional Chinese medicine Banxia Xiexin Decoction(BXD),which remarkedly enhanced the anti-proliferation activity of cyclophosphamide(CTX) on Hep G2 and SGC-7901 cell lines in vitro in our previous research.The aim of the study was to investigate the synergistic effects of HWKL and CTX using a transplanted H22 hepatocellular carcinoma mouse model.Methods:The CTX-toxic-reducing efficacy of HWKL was evalu...
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He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironment |
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| Jian-xiu Zhai,Ze-hai Song,Hang Chang,Yu-wei Wang,Na Han,Zhi-hui Liu,Jun Yin.He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironment[J].Chinese Herbal Medicines,2022,14(1):79-89. |
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| Authors: | Jian-xiu Zhai Ze-hai Song Hang Chang Yu-wei Wang Na Han Zhi-hui Liu Jun Yin |
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| Abstract: | Objective: He-Wei Granule (HWKL) is a modern product derived from the modified formulation of traditional Chinese medicine Banxia Xiexin Decoction (BXD), which remarkedly enhanced the anti-proliferation activity of cyclophosphamide (CTX) on HepG2 and SGC-7901 cell lines in vitro in our previous research. The aim of the study was to investigate the synergistic effects of HWKL and CTX using a transplanted H22 hepatocellular carcinoma mouse model.
Methods: The CTX-toxic-reducing efficacy of HWKL was evaluated by hematology indexes, organ indexes and marrow DNA detection. To investigate the underlying mechanisms, histopathology test, immunohistochemistry test and TUNEL staining were conducted. The efficacy of HWKL on the micro-vessel density (MVD) in tumor tissue was also evaluated by measuring CD34 level.
Results: High dose HWKL (6.75 g/kg) markedly attenuated CTX-induced hepatotoxicity and myelosuppression while significantly enhanced CTX anticancer efficacy in vivo. Further mechanism investigation suggested that high dose HWKL significantly increased cleaved Caspase 3 level and promoted apoptosis in tumor tissue by up-regulating Bax expression and down-regulating Bcl-2 and FasL expressions. Compared with CTX alone group, the decrease in LC-3B and Beclin 1 levels suggested that the autophagy in H22 carcinoma was significantly inhibited with addition of high dose HWKL. ELISA assay results indicated that the autophagy inhibition was achieved by decreasing p53 expression, blocking PI3K/AKT/mTOR pathway and recovering Th1/Th2 cytokine balance. In addition, CD34 and EGFR immunohistochemistry assay suggest that high dose HWKL could significantly decrease micro-vessel density (MVD) and inhibit angiogenesis in H22 carcinoma.
Conclusion: It could be concluded that high-dose HWKL enhanced CTX efficacy by promoting apoptosis, inhibiting autophagy and angiogenesis in tumor tissue while significantly alleviated CTX-induced toxicity, and could be applied along with CTX in clinical treatment as a supplement agent. |
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| Keywords: | cyclophosphamide He-Wei Granule H22 carcinoma synergistic effect toxicity |
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