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This study aims to investigate the inhibitory effects of cryptotanshinone (CPT) on colorectal cancer (CRC) both in vitro and in vivo, and to explore its potential mechanism of action based on ferroptosis. CRC HCT116 and HCT8 cells were treated with different concentrations of CPT. Cell counting, colony formation assays, and Annexin V/PI staining revealed that CPT significantly inhibited CRC cell viability and proliferation and promoted apoptosis. A CRC patient-derived organoid (PDO) (in accordance with the regulations of the Nankai University Biomedical Ethics Committee approval number NKUIRB2025036) model was established, and cell counting, hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC) detection of the tumor marker Ki67 confirmed that CPT suppressed PDO growth and malignant proliferation. A mouse xenograft tumor model was established (in compliance with the regulations of the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine, approval number: TCM-LAEC2025259K2011). Measurements of tumor volume and weight, HE staining, and Ki67 IHC demonstrated that CPT significantly inhibited tumor growth in vivo. Further studies found that a ferroptosis inhibitor could reverse the inhibitory effect of CPT on CRC cell proliferation, and CPT showed synergistic effects with ferroptosis inducers. Western blot and other detection results showed that CPT reduced the ratio of intracellular reduced glutathione (GSH) to oxidized glutathione (GSSG), and increased the levels of 4-hydroxynonenal (4-HNE) and the lipid peroxidation product malondialdehyde (MDA). Mechanistic studies indicated that CPT decreased glutathione peroxidase 4 (GPX4) mRNA levels and protein expression in a concentration-dependent manner. In conclusion, CPT can induce ferroptosis in CRC cells through GPX4, thereby inhibiting CRC cell proliferation and exerting anti-colorectal cancer effects.
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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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