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| Aidi Injection enhances radiosensitivity and inhibits migration of cervical cancer cells by regulating ADAMTS8-mediated β-catenin/c-Myc pathway |
| Hits 433 Download times 248 Received:February 19, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.08.15 |
| Key Words
Aidi Injection;ADAMTS8;cervical cancer;migration;radiosensitivity |
| Author Name | Affiliation | | HAN Duo | Department of Tumor Chemoradiotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China | | TIAN Fei | Department of Tumor Chemoradiotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China | | SHI Shuwei | Department of Tumor Chemoradiotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China | | PANG Dequan | Department of Tumor Chemoradiotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China | | NIE Qiuming | Department of Traditional Chinese Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China | | FAN Yumin | Department of Tumor Chemoradiotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China |
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| Abstract
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| [Objective] To investigate the effect of Aidi Injection on the migration and radiosensitization of cervical cancer cells by ADAM metallopeptidase with thrombospondin type 1 motif 8(ADAMTS8). [Methods] 1) Real-time quantitative PCR and Western blot were used to detect ADAMTS8 mRNA and protein levels in human cervical epithelial HcerEpic cells and cervical cancer SiHa and HeLa cells. 2) SiHa cells were cultured in media containing 0,1,5,10,30,and 50 mg/mL Aidi Injection,and cell proliferation was measured using the CCK-8 assay. 3) SiHa cells were divided into four groups:control(no treatment),10 mg/mL Aidi Injection(Aidi group),10 mg/mL Aidi Injection with negative control plasmid(Aidi+si-NC group),and 10 mg/mL Aidi Injection with ADAMTS8 silencing(Aidi+si-ADAMTS8 group). These groups were irradiated with 0,2,4,6,and 8 Gy using a medical linear accelerator. Clonogenic assays and the single-hit multi-target model were used to compare radiosensitivity. 4) All groups received a fixed 4 Gy irradiation dose,and cell migration was assessed using the Transwell assay. [Results] 1) ADAMTS8 mRNA and protein levels were significantly higher in HcerEpic cells compared to SiHa and HeLa cells(P<0.05). 2) Aidi Injection showed a more pronounced inhibitory effect on cell proliferation at concentrations between 0 and 10 mg/mL,while the inhibitory effect slowed between 10 and 50 mg/mL. 3) The levels of ADAMTS8 mRNA and protein were significantly higher in the Aidi group than in the control group,while were significantly lower in the Aidi+si-ADAMTS8 group than in the Aidi+si-NC group(P<0.05). Compared to the control group,the sensitization enhancement ratio(SER) of the Aidi group was 1.320;compared to the Aidi+si-NC group,the SER of the Aidi+si-ADAMTS8 group was 0.746. At an irradiation dose of 2 Gy,the protein levels of β-catenin and c-myelocytoma oncogene(c-Myc) were significantly lower in the Aidi group than in the control group,and significantly higher in the Aidi+si-ADAMTS8 group than in the Aidi+si-NC group(P<0.05). 4) The number of migrating cells and the protein levels of β-catenin and c-Myc were significantly lower in the Aidi group than in the control group,while significantly higher in the Aidi+si-ADAMTS8 group than in the Aidi+si-NC group(P<0.05). [Conclusion] Aidi Injection upregulates ADAMTS8 to inhibit the β-catenin/c-Myc pathway,suppressing migration and enhancing the radiosensitivity of SiHa cells. Silencing ADAMTS8 weakens those effects. |
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