Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells
Purpose Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PC...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | International Journal of Hyperthermia |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/02656736.2024.2335201 |
| _version_ | 1826902152881111040 |
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| author | Yajun Wu Pengyuan Liu Wendy Chen Shiting Bai Sisi Chen Jianglin Chen Xiaogang Xu Jindan Xia Yufei Wu Jianjun Lai Chuan Sun Zhenghong Lao Xiaoqing Wan Zhibing Wu |
| author_facet | Yajun Wu Pengyuan Liu Wendy Chen Shiting Bai Sisi Chen Jianglin Chen Xiaogang Xu Jindan Xia Yufei Wu Jianjun Lai Chuan Sun Zhenghong Lao Xiaoqing Wan Zhibing Wu |
| author_sort | Yajun Wu |
| collection | DOAJ |
| description | Purpose Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms.Methods We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors.Results Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups.Conclusion MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC. |
| first_indexed | 2024-04-24T12:32:38Z |
| format | Article |
| id | doaj.art-2856eb9f8da747f3922e18870ddc12cd |
| institution | Directory Open Access Journal |
| issn | 0265-6736 1464-5157 |
| language | English |
| last_indexed | 2025-02-17T07:35:16Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj.art-2856eb9f8da747f3922e18870ddc12cd2025-01-03T09:30:27ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572024-12-0141110.1080/02656736.2024.2335201Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cellsYajun Wu0Pengyuan Liu1Wendy Chen2Shiting Bai3Sisi Chen4Jianglin Chen5Xiaogang Xu6Jindan Xia7Yufei Wu8Jianjun Lai9Chuan Sun10Zhenghong Lao11Xiaoqing Wan12Zhibing Wu13Department of TCM Pharmacy, Zhejiang Hospital, Hangzhou, ChinaDepartment of Oncology, Zhejiang Hospital, Hangzhou, ChinaNanjing Drum Tower Hospital Group Suqian Hospital, Suqian, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaZhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaACS (International) Singapore, Singapore, SingaporeDepartment of Radiation Oncology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, ChinaDepartment of Oncology, People’s Hospital of Deqing County, Huzhou City, ChinaDepartment of TCM Pharmacy, Zhejiang Hospital, Hangzhou, ChinaDepartment of Oncology, Zhejiang Hospital, Hangzhou, ChinaPurpose Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms.Methods We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors.Results Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups.Conclusion MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.https://www.tandfonline.com/doi/10.1080/02656736.2024.2335201Microwave hyperthermiaradiosensitizationprostate cancerDNA damage responseROS |
| spellingShingle | Yajun Wu Pengyuan Liu Wendy Chen Shiting Bai Sisi Chen Jianglin Chen Xiaogang Xu Jindan Xia Yufei Wu Jianjun Lai Chuan Sun Zhenghong Lao Xiaoqing Wan Zhibing Wu Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells International Journal of Hyperthermia Microwave hyperthermia radiosensitization prostate cancer DNA damage response ROS |
| title | Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells |
| title_full | Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells |
| title_fullStr | Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells |
| title_full_unstemmed | Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells |
| title_short | Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells |
| title_sort | microwave hyperthermia enhances radiosensitization by decreasing dna repair efficiency and inducing oxidative stress in pc3 prostatic adenocarcinoma cells |
| topic | Microwave hyperthermia radiosensitization prostate cancer DNA damage response ROS |
| url | https://www.tandfonline.com/doi/10.1080/02656736.2024.2335201 |
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