Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT
The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect...
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Elsevier
2022-06-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222003961 |
| _version_ | 1811253511605714944 |
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| author | A-Lei Xu Yang-Yang Xue Wei-Tao Tao Si-Qi Wang Hui-Qin Xu |
| author_facet | A-Lei Xu Yang-Yang Xue Wei-Tao Tao Si-Qi Wang Hui-Qin Xu |
| author_sort | A-Lei Xu |
| collection | DOAJ |
| description | The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect when used alone in radiotherapy. The cytotoxicity of radiotherapy can be enhanced by modulating DNA repair, so new treatment options are being investigated to inhibit DNA repair pathways and sensitize tumors to radiation. Radiation induces DNA double-strand breaks (DSBs), and inhibition of Poly (ADP-Ribose) polymerase (PARP) can prevent the repair of these lesions. Hence, we evaluated the radiosensitization and the underlying mechanism of combination treatment with OA and olaparib in TNBC. Meanwhile, tumor hypoxia was monitored with 18F-Fluoroerythronitroimidazole (FETNIM) positron emission tomography/computed tomography (PET/CT) during radiosensitization therapy. Here, we found that OA and olaparib in combination with radiotherapy significantly inhibited cell proliferation compared with other groups. The results were observed using colony formation assays [sensitization enhancement ratios (SER) 1.16–1.65]. In vivo, tumor growth was significantly delayed in transplanted tumors receiving irradiation (IR) with OA and olaparib. 18F-FETNIM PET/CT can be utilized for tumor hypoxia monitoring and radiosensitization response evaluation. In conclusion, these results suggest that the combination of OA and olaparib with IR enhances the inhibition of MDA-MB-231 in cell culture and in mice, providing a potentially novel combination for the effective treatment of TNBC patients. |
| first_indexed | 2024-04-12T16:52:05Z |
| format | Article |
| id | doaj.art-c77daa64e5874bbfb602fe182d118617 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T16:52:05Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-c77daa64e5874bbfb602fe182d1186172022-12-22T03:24:21ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-06-01150113007Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CTA-Lei Xu0Yang-Yang Xue1Wei-Tao Tao2Si-Qi Wang3Hui-Qin Xu4Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Correspondence to: Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China.The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect when used alone in radiotherapy. The cytotoxicity of radiotherapy can be enhanced by modulating DNA repair, so new treatment options are being investigated to inhibit DNA repair pathways and sensitize tumors to radiation. Radiation induces DNA double-strand breaks (DSBs), and inhibition of Poly (ADP-Ribose) polymerase (PARP) can prevent the repair of these lesions. Hence, we evaluated the radiosensitization and the underlying mechanism of combination treatment with OA and olaparib in TNBC. Meanwhile, tumor hypoxia was monitored with 18F-Fluoroerythronitroimidazole (FETNIM) positron emission tomography/computed tomography (PET/CT) during radiosensitization therapy. Here, we found that OA and olaparib in combination with radiotherapy significantly inhibited cell proliferation compared with other groups. The results were observed using colony formation assays [sensitization enhancement ratios (SER) 1.16–1.65]. In vivo, tumor growth was significantly delayed in transplanted tumors receiving irradiation (IR) with OA and olaparib. 18F-FETNIM PET/CT can be utilized for tumor hypoxia monitoring and radiosensitization response evaluation. In conclusion, these results suggest that the combination of OA and olaparib with IR enhances the inhibition of MDA-MB-231 in cell culture and in mice, providing a potentially novel combination for the effective treatment of TNBC patients.http://www.sciencedirect.com/science/article/pii/S0753332222003961Triple-negative breast cancerOleanolic acidOlaparibRadiosensitizationPET/CT |
| spellingShingle | A-Lei Xu Yang-Yang Xue Wei-Tao Tao Si-Qi Wang Hui-Qin Xu Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT Biomedicine & Pharmacotherapy Triple-negative breast cancer Oleanolic acid Olaparib Radiosensitization PET/CT |
| title | Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT |
| title_full | Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT |
| title_fullStr | Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT |
| title_full_unstemmed | Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT |
| title_short | Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT |
| title_sort | oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18f fetnim micro pet ct |
| topic | Triple-negative breast cancer Oleanolic acid Olaparib Radiosensitization PET/CT |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222003961 |
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