Anti-gastric cancer activity in three-dimensional tumor spheroids of bufadienolides.
Multicellular spheroids of cancer cells have been increasingly used to screen anti-tumor compounds, owing to their in vivo like microenvironment and structure as well as compatibility to high-throughput/high-content screening. Here we report the potency and efficacy of a family of bufadienolides to inhibit the growth of gastric cancer cell line HGC-27 in three-dimensional (3D) spheroidal models. Examining the morphological and growth patterns of several cell lines in round-bottomed ultra-low attachment microplate suggested that HGC-27 cells formed reproducibly multicellular spheroidal structures. Profiling of 15 natural bufadienolides isolated from toad skin indicated that 8 14-hydroxy bufadienolides displayed inhibitory activity of the growth of HGC-27 spheroids in a dose-dependent manner. Notably, compared to clinical drugs taxol and epirubicin, active bufadienolides were found to penetrate more effectively into the HGC-27 spheroids, but with a narrower effective concentration range and a shorter lasting inhibitory effect. Furthermore, compared to two-dimensional (2D) cell monolayer assays, active bufadienolides exhibited weaker efficacy and different potency in 3D spheroid model, demonstrating the great potential of 3D multicellular cell spheroid models in anti-cancer drug discovery and development.
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Jixia
J
Wang
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226019, China.
Xiuli
X
Zhang
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Xiaolong
X
Li
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Yun
Y
Zhang
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Tao
T
Hou
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Lai
L
Wei
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Lala
L
Qu
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Liying
L
Shi
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Yanfang
Y
Liu
Department of Radiation Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.
Lijuan
L
Zou
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226019, China.
Xinmiao
X
Liang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002018:Bufanolides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D018874:Spheroids, Cellular / Q000187:drug effects*; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002018:Bufanolides