Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis
Background: Gastric cancer is the third leading cause of cancer-related death worldwide, for which several novel therapeutic strategies have been developed. Cisplatin (CDDP) mainly exerts its anti-gastric cancer effects; however, drug resistance limits its use. Thus, the development of drugs that ca...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023083184 |
| _version_ | 1797429896253800448 |
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| author | Chengwei Liu Dongchang Li Jian Wang Zhengguang Wang |
| author_facet | Chengwei Liu Dongchang Li Jian Wang Zhengguang Wang |
| author_sort | Chengwei Liu |
| collection | DOAJ |
| description | Background: Gastric cancer is the third leading cause of cancer-related death worldwide, for which several novel therapeutic strategies have been developed. Cisplatin (CDDP) mainly exerts its anti-gastric cancer effects; however, drug resistance limits its use. Thus, the development of drugs that can augment their antitumor effects is necessary. Arenobufagin (ArBu) is a novel anticancer drug, and the effects of ArBu in combination with CDDP on gastric cancer have not yet been studied. Aims: To identify a possible synergistic effect between ArBu and CDDP in gastric cancer and investigate the underlying mechanism. Methods: Cell viability, colony formation, migration, apoptosis, cell cycle, western blotting, immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR) were analyzed in vitro. Western blotting, RT-PCR, hematoxylin and eosin (H&E) staining and blood biochemistry were carried out to examine in vivo. Results: We found that ArBu, in combination with CDDP, effectively inhibited the proliferation and migration of gastric cancer cells, promoted apoptosis, and downregulated the expression of carbonic anhydrase 9 (CA9), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). In addition, treatment with ArBu in combination with CDDP increased the level of inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), E-cadherin, and nuclear factor kappa-B/p65 (NF-κB/p65). Furthermore, the combination of ArBu and CDDP inhibited tumor growth in xenograft nude mice with no obvious side effects. Conclusions: ArBu synergizes with CDDP to inhibit tumor growth both in vivo and in vitro by inducing alkaliptosis. This indicated that ArBu combined with CDDP may serve as a potential agent for the treatment of gastric cancer. |
| first_indexed | 2024-03-09T09:20:54Z |
| format | Article |
| id | doaj.art-2e326262d457468ea5b22b5fb9e0d020 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-09T09:20:54Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-2e326262d457468ea5b22b5fb9e0d0202023-12-02T07:01:15ZengElsevierHeliyon2405-84402023-11-01911e21110Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosisChengwei Liu0Dongchang Li1Jian Wang2Zhengguang Wang3Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR ChinaDepartment of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR ChinaDepartment of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR ChinaCorresponding author. Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, PR China.; Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR ChinaBackground: Gastric cancer is the third leading cause of cancer-related death worldwide, for which several novel therapeutic strategies have been developed. Cisplatin (CDDP) mainly exerts its anti-gastric cancer effects; however, drug resistance limits its use. Thus, the development of drugs that can augment their antitumor effects is necessary. Arenobufagin (ArBu) is a novel anticancer drug, and the effects of ArBu in combination with CDDP on gastric cancer have not yet been studied. Aims: To identify a possible synergistic effect between ArBu and CDDP in gastric cancer and investigate the underlying mechanism. Methods: Cell viability, colony formation, migration, apoptosis, cell cycle, western blotting, immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR) were analyzed in vitro. Western blotting, RT-PCR, hematoxylin and eosin (H&E) staining and blood biochemistry were carried out to examine in vivo. Results: We found that ArBu, in combination with CDDP, effectively inhibited the proliferation and migration of gastric cancer cells, promoted apoptosis, and downregulated the expression of carbonic anhydrase 9 (CA9), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). In addition, treatment with ArBu in combination with CDDP increased the level of inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), E-cadherin, and nuclear factor kappa-B/p65 (NF-κB/p65). Furthermore, the combination of ArBu and CDDP inhibited tumor growth in xenograft nude mice with no obvious side effects. Conclusions: ArBu synergizes with CDDP to inhibit tumor growth both in vivo and in vitro by inducing alkaliptosis. This indicated that ArBu combined with CDDP may serve as a potential agent for the treatment of gastric cancer.http://www.sciencedirect.com/science/article/pii/S2405844023083184ArenobufaginCisplatinGastric cancerAlkaliptosis |
| spellingShingle | Chengwei Liu Dongchang Li Jian Wang Zhengguang Wang Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis Heliyon Arenobufagin Cisplatin Gastric cancer Alkaliptosis |
| title | Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis |
| title_full | Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis |
| title_fullStr | Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis |
| title_full_unstemmed | Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis |
| title_short | Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis |
| title_sort | arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis |
| topic | Arenobufagin Cisplatin Gastric cancer Alkaliptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023083184 |
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