Full
Outline
To investigate the effect of Guben Qingyuan Prescription（固本清源方）on inhibiting cancer-associated fibroblast（CAF） in the development of resistance to enzalutamide.
A tumor-bearing mouse model of enzalutamide-resistant prostate cancer cells was established to observe the effects of Guben Qingyuan Prescription combined with enzalutamide on tumor growth and CAF in tumor tissues. The effects of Guben Qingyuan Prescription on CAF transformation were assessed using immunofluorescence. CAF proliferation was evaluated by the CCK8 assay, and the influence of Guben Qingyuan Prescription on CAF-derived factors was measured via enzyme-linked immunosorbent assay（ELISA）.
The tumor inhibition rate of the Guben Qingyuan Prescription combined with enzalutamide ranged from 29% to 47%. In the medium - and high-dose groups, the combination treatment showed a statistically significant difference compared to the enzalutamide-only group（P<0.01）. Immunofluorescence and immunohistochemistry results demonstrated that the expressions of CAF markers fibroblast activation protein-α（FAP）and α-smooth muscle actin（α-SMA）in tumor tissues of enzalutamide-resistant mice were significantly higher than those in the group inoculated with prostate cancer C4-2B cells. The medium - and high-dose Guben Qingyuan Prescription combined with enzalutamide groups significantly inhibited the expressions of FAP and α-SMA compared to the enzalutamide-only group（P<0.05）. Additionally, immunofluorescence showed that serum containing medium - and high-dose Guben Qingyuan Prescription groups could inhibit the expressions of FAP and α-SMA in vitro. After 48 and 72 hours of treatment, the inhibition rates of the medium - and high-dose Guben Qingyuan Prescription groups significantly increased, with a statistically significant difference compared to the control group（P<0.05）. Further studies revealed that Guben Qingyuan Prescription reduced the concentrations of transforming growth factor-β1（TGF-β1）, tumor necrosis factor-α（TNF-α）, stromal cell-derived factor-1（SDF-1）, Wingless/Integrated-3a（Wnt3a）and matrix metalloproteinase 2（MMP2）in CAF supernatants.
Guben Qingyuan Prescription has a significant effect in delaying resistance to enzalutamide, a novel endocrine therapy for prostate cancer, and its mechanism of action may be related to the inhibition of CAF.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 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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