Dataset Information

Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis.

ABSTRACT:

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.

SUBMITTER: Liu C

PROVIDER: S-EPMC10618551 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis.

Liu Chengwei C Li Dongchang D Wang Jian J Wang Zhengguang Z

Heliyon 20231019 11

<h4>Background</h4>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.<h4> ...[more]

PMID: 37920505

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Project description:BackgroundsAs previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms.MethodsWe performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues.ResultsThe cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3' untranslated region (3'UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells.ConclusionsTaken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

Dataset Information

Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis.

Background

Aims

Methods

Results

Conclusions

Publications

Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis.

Similar Datasets

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