Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway
Abstract Background Colorectal cancer is a common malignant tumour. Invasive growth and distant metastasis are the main characteristics of its malignant biological behaviour, and they are also the primary factors leading to death in colon cancer patients. Atovaquone is an antimalarial drug, and its...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11585-9 |
| _version_ | 1797630179459203072 |
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| author | Bin Liu Xin Zheng Jiajun Li Peng Yao Peng Guo Wei Liu Gaoping Zhao |
| author_facet | Bin Liu Xin Zheng Jiajun Li Peng Yao Peng Guo Wei Liu Gaoping Zhao |
| author_sort | Bin Liu |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer is a common malignant tumour. Invasive growth and distant metastasis are the main characteristics of its malignant biological behaviour, and they are also the primary factors leading to death in colon cancer patients. Atovaquone is an antimalarial drug, and its anticancer effect has recently been demonstrated in several cancer models in vitro and in vivo, but it has not been examined in the treatment of colorectal cancer. Methods To elucidate the effect of atovaquone on colorectal cancer. We used RNA transcriptome sequencing, RT‒PCR and Western blot experiments to examine the expression of NF-κB (p-P65), EMT-related proteins and related inflammatory factors (IL1B, IL6, CCL20, CCL2, CXCL8, CXCL6, IL6ST, FAS, IL10 and IL1A). The effect of atovaquone on colorectal cancer metastasis was validated using an animal model of lung metastases. We further used transcriptome sequencing, the GCBI bioinformatics database and the STRING database to predict relevant target proteins. Furthermore, pathological sections were collected from relevant cases for immunohistochemical verification. Results This study showed that atovaquone could inhibit colorectal cancer metastasis and invasion in vivo and in vitro, inhibit the expression of E-cadherin protein, and promote the protein expression of N-cadherin, vimentin, ZEB1, Snail and Slug. Atovaquone could inhibit EMT by inhibiting NF-κB (p-P65) and related inflammatory factors. Further bioinformatics analysis and verification showed that PDGFRβ was one of the targets of atovaquone. Conclusion In summary, atovaquone can inhibit the expression of NF-κB (p-P65) and related inflammatory factors by inhibiting the protein expression of p-PDGFRβ, thereby inhibiting colorectal cancer metastasis. Atovaquone may be a promising drug for the treatment of colorectal cancer metastasis. |
| first_indexed | 2024-03-11T11:04:31Z |
| format | Article |
| id | doaj.art-960d51c6e7db42cea27efc51955ff226 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-11T11:04:31Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-960d51c6e7db42cea27efc51955ff2262023-11-12T12:20:21ZengBMCBMC Cancer1471-24072023-11-0123111310.1186/s12885-023-11585-9Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathwayBin Liu0Xin Zheng1Jiajun Li2Peng Yao3Peng Guo4Wei Liu5Gaoping Zhao6Department of General Surgery, The Second Affiliated Hospital of Chengdu Medical College, National Nuclear Corporation 416 HospitalDepartment of General Surgery, The Second Affiliated Hospital of Chengdu Medical College, National Nuclear Corporation 416 HospitalDepartment of General Surgery, The Second Affiliated Hospital of Chengdu Medical College, National Nuclear Corporation 416 HospitalDepartment of Nephrology, The Second Affiliated Hospital of Chengdu Medical College, National Nuclear Corporation 416 HospitalChengdu Medical CollegeDepartment of General Surgery, The Second Affiliated Hospital of Chengdu Medical College, National Nuclear Corporation 416 HospitalDepartment of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s HospitalAbstract Background Colorectal cancer is a common malignant tumour. Invasive growth and distant metastasis are the main characteristics of its malignant biological behaviour, and they are also the primary factors leading to death in colon cancer patients. Atovaquone is an antimalarial drug, and its anticancer effect has recently been demonstrated in several cancer models in vitro and in vivo, but it has not been examined in the treatment of colorectal cancer. Methods To elucidate the effect of atovaquone on colorectal cancer. We used RNA transcriptome sequencing, RT‒PCR and Western blot experiments to examine the expression of NF-κB (p-P65), EMT-related proteins and related inflammatory factors (IL1B, IL6, CCL20, CCL2, CXCL8, CXCL6, IL6ST, FAS, IL10 and IL1A). The effect of atovaquone on colorectal cancer metastasis was validated using an animal model of lung metastases. We further used transcriptome sequencing, the GCBI bioinformatics database and the STRING database to predict relevant target proteins. Furthermore, pathological sections were collected from relevant cases for immunohistochemical verification. Results This study showed that atovaquone could inhibit colorectal cancer metastasis and invasion in vivo and in vitro, inhibit the expression of E-cadherin protein, and promote the protein expression of N-cadherin, vimentin, ZEB1, Snail and Slug. Atovaquone could inhibit EMT by inhibiting NF-κB (p-P65) and related inflammatory factors. Further bioinformatics analysis and verification showed that PDGFRβ was one of the targets of atovaquone. Conclusion In summary, atovaquone can inhibit the expression of NF-κB (p-P65) and related inflammatory factors by inhibiting the protein expression of p-PDGFRβ, thereby inhibiting colorectal cancer metastasis. Atovaquone may be a promising drug for the treatment of colorectal cancer metastasis.https://doi.org/10.1186/s12885-023-11585-9AtovaquoneColorectal cancerMetastasisPDGFRβNF-κB |
| spellingShingle | Bin Liu Xin Zheng Jiajun Li Peng Yao Peng Guo Wei Liu Gaoping Zhao Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway BMC Cancer Atovaquone Colorectal cancer Metastasis PDGFRβ NF-κB |
| title | Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway |
| title_full | Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway |
| title_fullStr | Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway |
| title_full_unstemmed | Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway |
| title_short | Atovaquone inhibits colorectal cancer metastasis by regulating PDGFRβ/NF-κB signaling pathway |
| title_sort | atovaquone inhibits colorectal cancer metastasis by regulating pdgfrβ nf κb signaling pathway |
| topic | Atovaquone Colorectal cancer Metastasis PDGFRβ NF-κB |
| url | https://doi.org/10.1186/s12885-023-11585-9 |
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