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Anti-tumor activity and mechanisms of isorhamnetin in combination with sorafenib for renal cancer
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Qian-qian DU, Lu-lu HUANG, Chun-xia LIU, Mei TANG, Chen YAN, Yan LI*
Acta Pharmaceutica Sinica | 2019, 54(8) : 1424 - 1430
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Acta Pharmaceutica Sinica | 2019, 54(8): 1424-1430
Original Articles
Anti-tumor activity and mechanisms of isorhamnetin in combination with sorafenib for renal cancer
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Qian-qian DU, Lu-lu HUANG, Chun-xia LIU, Mei TANG, Chen YAN, Yan LI*
Affiliations
  • Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2019-08-12 doi: 10.16438/j.0513-4870.2018-1138
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This study aimed to explore the anti-tumor activity and mechanisms of action of isorhamnetin, a compound isolated from Astragalus membranaceus, in combination with sorafenib for treatment of renal cell carcinoma (RCC). The anti-tumor activity of isorhamnetin in combination with sorafenib was detected by MTT assay with cells in culture or Renca xenograft model in mice. Western blot was used to study the mechanisms of isorhamnetin in combination with sorafenib. Lymphocyte proliferation assay was also used to investigate the effects of the two drugs in combination. The results indicated that isorhamnetin inhibited the proliferation of RCC cells, with IC50 for A498, 786-O and Renca cell lines with being 31.7, 28.8 and 106.0 μmol·L-1, respectively. Isorhamnetin in combination with sorafenib improved the anti-lymphocyte proliferation activity of sorafenib with the IC50 down to 12.0 μmol·L-1. Isorhamnetin inhibited the growth of RCC in mice slightly with the inhibition efficiency at 26.9%. With 50.0 mg·kg-1 isorhamnetin in combination with 20.0 mg·kg-1 sorafenib, the anti-tumor activity of sorafenib was enhanced, with inhibition of growth rate increased to 60.7%. Meanwhile, isorhamnetin in combination with sorafenib could promote the lymphocytes proliferation in Renca xenograft model. Western blot results showed that combination of isorhamnetin and sorafenib could inhibit c-Raf/MEK/ERK and AKT/mTOR signaling pathways. In conclusion, the combination of isorhamnetin with sorafenib could increase the anti-tumor activity of sorafenib in RCC in vitro and in vivo. The mechanisms may be related to the inhibition of c-Raf/MEK/ERK and AKT/mTOR signaling pathways. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.

isorhamnetin  /  sorafenib  /  drug combination  /  renal cancer  /  c-Raf/MEK/ERK  /  AKT/mTOR
Qian-qian DU, Lu-lu HUANG, Chun-xia LIU, Mei TANG, Chen YAN, Yan LI. Anti-tumor activity and mechanisms of isorhamnetin in combination with sorafenib for renal cancer[J]. Acta Pharmaceutica Sinica, 2019 , 54 (8) : 1424 -1430 . DOI: 10.16438/j.0513-4870.2018-1138
Year 2019 volume 54 Issue 8
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Article Info
doi: 10.16438/j.0513-4870.2018-1138
  • Receive Date:2018-12-21
  • Online Date:2026-01-26
  • Published:2019-08-12
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  • Received:2018-12-21
  • Revised:2019-01-04
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    Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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