1. Academic Validation
  2. Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis through miR-497-5p/AKT3 axis

Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis through miR-497-5p/AKT3 axis

  • Cancer Cell Int. 2020 Aug 7;20:379. doi: 10.1186/s12935-020-01468-5.
Zi-Yuan Nie  # 1 Ming-Hui Zhao  # 2 Bao-Qian Cheng 3 Rong-Fang Pan 4 Tian-Rui Wang 5 Yan Qin 6 7 Xue-Jun Zhang 1
Affiliations

Affiliations

  • 1 Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000 China.
  • 2 Department of Radiology, Affiliated Hospital of Hebei University, Baoding, 071000 China.
  • 3 Department of Clinical Medicine, Hebei Medical University, Shijiazhuang, 050000 China.
  • 4 Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266003 China.
  • 5 Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051 China.
  • 6 Central Laboratory, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000 China.
  • 7 Department of Life Science and Green Development, Hebei University, Baoding, 071000 China.
  • # Contributed equally.
Abstract

Background: The roots of Salvia miltiorrhiza are used in traditional Chinese medicine (TCM) and have high medicinal value. Tanshinone IIA (Tan IIA) is the active ingredient of Salvia miltiorrhiza which can inhibit the growth of acute leukemia cell lines in vitro, although the mechanism remains unclear.

Methods: CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability. Western blot analysis was used to detect protein expression. miR-497-5p expression level was detected by using qRT-PCR, and Annexin V-FITC/propidium iodide (PI) was used to detect cell Apoptosis.

Results: Here we reported that Tan IIA could inhibit cell proliferation, induce cell cycle arrest, and promote cell Apoptosis in acute myeloid leukemia (AML) cells. Thus, Tan IIA had the anti-cancer activity in AML cell lines, which was likely mediated by up-regulation of miR-497-5p expression. Our data further showed that in AML cells, the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic. We demonstrated that Tan IIA could inhibit the expression of Akt3 by up-regulating the expression of miR-497-5p. We subsequently identified that Akt3 was the direct target of miR-497-5p, and that treatment with Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions. In turn, PCNA expression was increased and cleaved Caspase-3 was suppressed, which contributed to the growth of AML cells.

Conclusions: Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated Akt3 downregulation pathway.

Keywords

AKT3; Acute myeloid leukemia; Apoptosis; Proliferation; Tanshinone IIA; miR-497-5p.

Figures
Products