Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells
Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely...
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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 |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/02656736.2024.2310017 |
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| author | Bor-Chyuan Su Guan-Yu Chen Chun-Ming Yang Wei-Ting Chuang Meng-Chieh Lin Pei-Ling Hsu Chu-Wan Lee Chih-Cheng Cheng Shih-Ying Wu Bo-Syong Pan Hsin-Hsien Yu |
| author_facet | Bor-Chyuan Su Guan-Yu Chen Chun-Ming Yang Wei-Ting Chuang Meng-Chieh Lin Pei-Ling Hsu Chu-Wan Lee Chih-Cheng Cheng Shih-Ying Wu Bo-Syong Pan Hsin-Hsien Yu |
| author_sort | Bor-Chyuan Su |
| collection | DOAJ |
| description | Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC. |
| format | Article |
| id | doaj-art-7e11e6d856f549419c5afef5b0e23846 |
| institution | Kabale University |
| issn | 0265-6736 1464-5157 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj-art-7e11e6d856f549419c5afef5b0e238462025-01-03T09:30:28ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572024-12-0141110.1080/02656736.2024.2310017Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cellsBor-Chyuan Su0Guan-Yu Chen1Chun-Ming Yang2Wei-Ting Chuang3Meng-Chieh Lin4Pei-Ling Hsu5Chu-Wan Lee6Chih-Cheng Cheng7Shih-Ying Wu8Bo-Syong Pan9Hsin-Hsien Yu10Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanDepartment of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Nursing, National Tainan Junior College of Nursing, Tainan, TaiwanDivision of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston-Salem, NC, USADepartment of Pathology, Duke University School of Medicine, Durham, NC, USATMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, TaiwanObjective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC.https://www.tandfonline.com/doi/10.1080/02656736.2024.2310017Hyperthermiastomach cancerchemosensitivityimmune checkpoints |
| spellingShingle | Bor-Chyuan Su Guan-Yu Chen Chun-Ming Yang Wei-Ting Chuang Meng-Chieh Lin Pei-Ling Hsu Chu-Wan Lee Chih-Cheng Cheng Shih-Ying Wu Bo-Syong Pan Hsin-Hsien Yu Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells International Journal of Hyperthermia Hyperthermia stomach cancer chemosensitivity immune checkpoints |
| title | Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells |
| title_full | Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells |
| title_fullStr | Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells |
| title_full_unstemmed | Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells |
| title_short | Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells |
| title_sort | impacts of hyperthermic chemotherapeutic agent on cytotoxicity chemoresistance related proteins and pd l1 expression in human gastric cancer cells |
| topic | Hyperthermia stomach cancer chemosensitivity immune checkpoints |
| url | https://www.tandfonline.com/doi/10.1080/02656736.2024.2310017 |
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