Effects of different combined regimens of cisplatin, metformin, and quercetin on nasopharyngeal carcinoma cells and subcutaneous xenografts

Chen, Zhongwei; Zeng, Zhen; Zhu, Shanshan; Zeng, Ying; Lin, Qi; Luo, Liang; Han, Xuan

doi:10.1038/s41598-020-80198-0

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…An epidemiologic analysis based on three multicentric studies showed that metformin given for the treatment of diabetes is associated with longer overall survival of patients with HNSCC despite the negative prognostic impact of diabetes itself ( 57 ). In addition, it was demonstrated that the combination of metformin and cisplatin significantly improved the therapeutic effect of cisplatin in OSCC ( 58 ) and NPC ( 59 ). In contrast, another study found no significant prognostic impact of metformin in patients with HNSCC ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression

Abou Kors,

Hofmann,

Betzler

et al. 2024

Cancer Research Communications

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Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those with HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate HPV-negative from -positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA from 23 HPV-negative and 39 -positive OPSCC tumors (n = 62) was sequenced to uncover the transcriptomic profiles. Differential expression followed by gene set enrichment analysis was performed to outline the top enriched biological process in the HPV-negative compared to -positive entity. INHBA, the highest overexpressed gene in the HPV-negative tumor, was knocked down. Functional assays (migration, proliferation, cell death, stemness) were conducted to confirm the target’s oncogenic role. Correlation analyses to reveal its impact on the tumor microenvironment were performed. We revealed that epithelial-to-mesenchymal transition (EMT) is the most enriched process in HPV-negative compared to -positive OPSCC, with INHBA (inhibin beta A subunit) being the top upregulated gene. INHBA knockdown downregulated the expression of EMT transcription factors and attenuated migration, proliferation, stemness, and cell death resistance of OPSCC cells. We uncovered that INHBA associates with a pro-tumor microenvironment by negatively correlating with anti-tumor CD8+ T and B cells while positively correlating with pro-tumor M1 macrophages. We identified three miRNAs that are putatively involved in repressing INHBA expression. Our results indicate that the upregulation of INHBA is tumor-promoting. We propose INHBA as an attractive therapeutic target for the treatment of INHBA-enriched tumors in HPV-negative OPSCC patients to ameliorate prognosis.

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Section: Discussionmentioning

confidence: 99%

INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression

Abou Kors,

Hofmann,

Betzler

et al. 2024

Cancer Research Communications

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“…Cisplatin-based chemotherapeutic regimens are applied as adjuvant treatments against OS patients, especially for malignancies with aggressive characteristics [12,13]. Notwithstanding, Cisplatin resistance is a significant hindrance to its clinical application.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Quercetin in Increasing the Rate of Cisplatin-Induced Apoptosis Via the NF-κB Pathway in MG-63 Cancer Cells

et al. 2022

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Introduction Numerous studies suggest that the co-treatment of chemotherapeutic agents with flavonoids such as Quercetin (Que) may enhance tumor cells’ susceptibility to these agents. Hence, in the current study, we investigated Que’s role in combination with Cisplatin to promote cell apoptosis by focusing on the NF-κB signaling pathway in the osteosarcoma cell lines. Methods The Que, Cisplatin, and their combination’s general cytotoxicity effects were evaluated using an MTT assay for 72 hrs. The protein expression levels of NF-κB were detected by an enzyme-linked immunosorbent assay (ELISA) Kit. Flow cytometry was used to evaluate cell apoptosis. Results Que considerably elevated the cytotoxicity of Cisplatin (P<0.05). Que also dramatically down-regulated the expression levels of NF-κB in MG-63 cells compared to mono-treatment (P<0.05). Besides, Que promotes cisplatin-induced apoptosis in MG-63 cells. Conclusion Our study’s findings provide an exact point in the field of adjuvant therapy in osteosarcoma. In other words, this study could provide new insights into a better understanding of the role of Que in elevating cisplatin-induced apoptosis with NF-κB down-regulation.

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“…In epidemiological studies of head and neck cancer, diabetic patients treated with metformin had a lower risk of HNSCC than those who were not treated with metformin 11 . In addition, metformin potentiates the therapeutic effect of cisplatin on nonsmall-cell lung cancer 12 , breast cancer 13 , nasopharyngeal cancer 14 and oral squamous cell carcinoma 15 .…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic Analysis of Transcriptome Changes Underlying Metformin-induced Reversal of Drug Resistance in Head and Neck Squamous Cell Carcinoma Cells

hou

Li²,

Jin³

et al. 2021

Preprint

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Background: Metformin is the first-line drug for type II diabetes, and recent studies indicate that metformin plays an inhibitory role in multiple cancers. Metformin can also enhance the effect of chemotherapy. Although head and neck squamous cell carcinoma cells are sensitive to metformin, the mechanisms related to the metformin response and the chemosensitization effect have not been fully studied. Results: In this study, we aimed to elucidate the molecular mechanisms of metformin in HNSCC by transcriptome analysis and to reveal the underlying mechanisms of the sensitizing effects of metformin by combined online dataset analysis. mRNA sequencing and functional analysis of HNSCC samples after metformin treatment and functional analysis of mRNAs with opposite metformin-induced effects in chemosensitive versus chemoresistant cells revealed the molecular pathways, mainly the base excision repair pathway, by which this small molecule drug sensitizes HNSCC cells to treatment. Conclusions: These findings indicate that metformin exerts a hypersensitization effect by regulating the BER pathway in tumour cells, reducing their self-repair capacity after chemotherapy-induced DNA damage. In addition, the genes identified by transcriptome analysis are candidates for further investigation into the effector targets of metformin in the inhibition of HNSCC and could be applied to improve the treatment in HNSCC patients who develop resistance after advanced chemotherapy.

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Effects of different combined regimens of cisplatin, metformin, and quercetin on nasopharyngeal carcinoma cells and subcutaneous xenografts

Cited by 7 publications

References 41 publications

INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression

INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression

Investigating the Role of Quercetin in Increasing the Rate of Cisplatin-Induced Apoptosis Via the NF-κB Pathway in MG-63 Cancer Cells

Bioinformatic Analysis of Transcriptome Changes Underlying Metformin-induced Reversal of Drug Resistance in Head and Neck Squamous Cell Carcinoma Cells

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