{"title":"PAKs抑制剂IPA-3和PF-3758309联合使用可通过干扰DNA损伤反应有效抑制结肠癌细胞生长。","authors":"Muzaffer Dukel, Kayahan Fiskin","doi":"10.1080/09553002.2022.2110326","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>PAKs proteins are speculated as new promising targets for cancer therapy due to their central role in many oncogenic pathways. Because PAKs proteins are very significant during carcinogenesis, we aimed to investigate the hypothesis that inhibition of PAKs with IPA-3 and PF-3758309 treatment could synergistically reduce colon carcinoma cell growth.</p><p><strong>Materials and methods: </strong>The cytotoxic effects of both drugs were determined by a cell viability assay. Cell cycle and apoptosis were analyzed by flow cytometry. The effects of inhibitor drugs on marker genes of apoptosis, autophagy, cell cycle, and DNA damage were tested via immunoblotting.</p><p><strong>Results and conclusions: </strong>We found out the synergistic effect of these drugs in pair on five colon cancer cell lines. Combined treatment with IPA-3+PF-3758309 in SW620 and Colo 205 cells markedly suppressed colon formation and induced apoptosis, cell cycle arrest, and autophagy compared with treatment with each drug alone. Additionally, this combination sensitized colon cancer cells to ionizing radiation that resulted in inhibition of cell growth.</p><p><strong>Significance: </strong>Collectively, our findings show for the first time that cotreatment of IPA-3 with PF-3758309 exhibits superior inhibitory effects on colon carcinoma cell growth via inducing DNA damage-related cell death and also enforces a cell cycle arrest.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Combination of PAKs inhibitors IPA-3 and PF-3758309 effectively suppresses colon carcinoma cell growth by perturbing DNA damage response.\",\"authors\":\"Muzaffer Dukel, Kayahan Fiskin\",\"doi\":\"10.1080/09553002.2022.2110326\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>PAKs proteins are speculated as new promising targets for cancer therapy due to their central role in many oncogenic pathways. Because PAKs proteins are very significant during carcinogenesis, we aimed to investigate the hypothesis that inhibition of PAKs with IPA-3 and PF-3758309 treatment could synergistically reduce colon carcinoma cell growth.</p><p><strong>Materials and methods: </strong>The cytotoxic effects of both drugs were determined by a cell viability assay. Cell cycle and apoptosis were analyzed by flow cytometry. The effects of inhibitor drugs on marker genes of apoptosis, autophagy, cell cycle, and DNA damage were tested via immunoblotting.</p><p><strong>Results and conclusions: </strong>We found out the synergistic effect of these drugs in pair on five colon cancer cell lines. Combined treatment with IPA-3+PF-3758309 in SW620 and Colo 205 cells markedly suppressed colon formation and induced apoptosis, cell cycle arrest, and autophagy compared with treatment with each drug alone. Additionally, this combination sensitized colon cancer cells to ionizing radiation that resulted in inhibition of cell growth.</p><p><strong>Significance: </strong>Collectively, our findings show for the first time that cotreatment of IPA-3 with PF-3758309 exhibits superior inhibitory effects on colon carcinoma cell growth via inducing DNA damage-related cell death and also enforces a cell cycle arrest.</p>\",\"PeriodicalId\":14261,\"journal\":{\"name\":\"International Journal of Radiation Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/09553002.2022.2110326\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09553002.2022.2110326","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
Combination of PAKs inhibitors IPA-3 and PF-3758309 effectively suppresses colon carcinoma cell growth by perturbing DNA damage response.
Purpose: PAKs proteins are speculated as new promising targets for cancer therapy due to their central role in many oncogenic pathways. Because PAKs proteins are very significant during carcinogenesis, we aimed to investigate the hypothesis that inhibition of PAKs with IPA-3 and PF-3758309 treatment could synergistically reduce colon carcinoma cell growth.
Materials and methods: The cytotoxic effects of both drugs were determined by a cell viability assay. Cell cycle and apoptosis were analyzed by flow cytometry. The effects of inhibitor drugs on marker genes of apoptosis, autophagy, cell cycle, and DNA damage were tested via immunoblotting.
Results and conclusions: We found out the synergistic effect of these drugs in pair on five colon cancer cell lines. Combined treatment with IPA-3+PF-3758309 in SW620 and Colo 205 cells markedly suppressed colon formation and induced apoptosis, cell cycle arrest, and autophagy compared with treatment with each drug alone. Additionally, this combination sensitized colon cancer cells to ionizing radiation that resulted in inhibition of cell growth.
Significance: Collectively, our findings show for the first time that cotreatment of IPA-3 with PF-3758309 exhibits superior inhibitory effects on colon carcinoma cell growth via inducing DNA damage-related cell death and also enforces a cell cycle arrest.
期刊介绍：
The International Journal of Radiation Biology publishes original papers, reviews, current topic articles, technical notes/reports, and meeting reports on the effects of ionizing, UV and visible radiation, accelerated particles, electromagnetic fields, ultrasound, heat and related modalities. The focus is on the biological effects of such radiations: from radiation chemistry to the spectrum of responses of living organisms and underlying mechanisms, including genetic abnormalities, repair phenomena, cell death, dose modifying agents and tissue responses. Application of basic studies to medical uses of radiation extends the coverage to practical problems such as physical and chemical adjuvants which improve the effectiveness of radiation in cancer therapy. Assessment of the hazards of low doses of radiation is also considered.
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