Effects of HOXD10 on the mechanism of cordycepin action in different types of human breast cancer cells

Objective We investigate the molecular mechanism underlying inhibitory effects of cordycepin on proliferation, apoptosis, migration and invasion of breast cancer. We focus on the role of HOXD10 in inhibitory effects of cordycepin. Methods Two individual breast cancer cell lines, MCF-7 and MDA-MB-231, were used in this study to investigate the effects of cordycepin on proliferation, apoptosis, migration and invasion of breast cancer, by cell counting kit-8 (CCK-8) assays, flow cytometry and Transwell assays. The small interfering RNAs (siRNAs) targeted HOXD10 were transfected into MCF-7 and MDA-MB-231 cells to knock down HOXD10. We investigate the role of HOXD10 by comparing the difference between group NC and group siRNAs. Results The A values of cordycepin treated MCF-7 and MDA-MB-231 cells were significantly lower than those of control group (DMSO group) (MCF-7cells: 0.665±0.004 vs. 0.733±0.005, t=10.450, and MDA-MB-231cells: 0.632±0.005 vs. 0.722±0.005, t=13.330, P<0.05), which means the proliferation of breast cancer cells was significantly inhibited, The apoptosis rateof cordycepin treated MCF-7 and MDA-MB-231 cells were significantly higher than those of control group (MCF-7cells: 20.200±0.322 vs. 5.500±0.000, t=45.730, MDA-MB-231cells: 21.800±1.493 vs. 5.367±0.318, t=10.760, P<0.05). There were significantly fewer migrated MCF-7 and MDA-MB-231 cells in cordycepin group than in control group(MCF-7 cells: 28.670±1.764 vs. 83.330±2.186, t=19.460, MDA-MB-231cells: 29.000±2.646 vs. 114.700±3.180, t=20.710, P<0.05). There were significantly fewer invasive MCF-7 and MDA-MB-231 cells in cordycepin group than control group(MCF-7cells: 24.670±2.603 vs. 49.000±1.528, t=8.0620, MDA-MB-231cells: 12.330±1.453 vs. 36.670±2.728, t=7.872, P<0.05). After transfection of MCF-7 and MDA-MB-231 cells with siRNA and intervention with cordycepin, the proliferation of breast cancer cells was inhibited (MCF-7cells: 0.627±0.004 vs. 0.648±0.006, t=2.951, MDA-MB-23 cells: 0.620±0.006 vs. 0.635±0.004, t=2.087, P<0.05). The apoptosis rate of the treatment group was significantly higher than the control group (MCF-7 cells: 20.470±0.260 vs. 16.300±0.153, t=13.800, MDA-MB-23 cells: 19.170±0.167 vs. 17.030±0.186, t=8.5520, P<0.05). There were significantly fewer migrated MCF-7 and MDA-MB-231 cells in siRNA group than in control group(MCF-7cells: 11.000±2.082 vs. 30.330±2.028, t=6.653, MDA-MB-23cells: 11.330±1.4530 vs. 23.000±1.528, t=5.534, P<0.05). There were significantly fewer invasive MCF-7 and MDA-MB-231cells in siRNA group than control group(MCF-7 cells: 16.330±1.764 vs. 23.670±1.760, t=2.940, MDA-MB-2 cells: 9.333±1.453 vs. 19.670±2.333, t=3.759, P<0.05). Those values above are statistically significant. Conclusion Cordycepin induces apoptosis and inhibits proliferation, migration and invasion of breast cancer.2. Suppression of HOXD10 promptes the effects of cordycepin on proliferation, apoptosis, migration and invasion of breast cancer. Key words: Cordycepin; HOXD10; Breast cancer; Signaling pathway