Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma

Sep 21, 2026

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Aim: determine how sirtuin1 (sirt1) influences esophageal squamous cell carcinoma (ESCC) chemosensitivity to cisplatin. Methods: ESCC cell ablation was used to establish a xenograft mouse tumor model; tumor volume was measured, and sirt1 levels were assessed in patients and cells. Results: sirt1 overexpression correlated with ESCC, while sirt1 knockdown increased cisplatin sensitivity. Glycolysis linked to cisplatin resistance, and sirt1 enhanced chemosensitivity via HK2 in vitro and in vivo. Conclusion: sirt1 knockdown regulates glycolysis pathway activity and improves ESCC cisplatin response.

LanguageEnglish

CategoryHealthcare

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Pages11

Reading Time28 min

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ABSTRACT

Introduction

Results

Increased sirt1 expression in ESCC cells and tissues

Sirt1 knockdown prevents ESCC cell proliferation and promotes cell apoptosis

CANCER BIOLOGY & THERAPY 2024, VOL. 25, NO. 1, 2365449 [https://doi.org/10.1080/15384047.2024.2365449](https://doi.org/10.1080/15384047.2024.2365449) RESEARCH PAPER Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma Xuewen Yanga, Shisen Lia, Chunsheng Xua, Shushang Liua, Xiang Zhanga, Bo Lianb, and Mengbin Li a aGastrointestinal Surgery Department, The First Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, China; bClinical Nutrition Department, The First Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, China ABSTRACT We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells’ cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity. ARTICLE HISTORY Received 17 March 2024 Revised 2 June 2024 Accepted 4 June 2024 KEYWORDS Esophageal squamous cell carcinoma; glycolysis; cisplatin; chemosensitivity; sirt1 Introduction EC (esophageal cancer) is a digestive system’s malignant cancer in the world. Principal pathological kind is ESCC (esophageal squamous cell carcinoma) . 1 At present, there are many therapeutic drugs for ESCC, such as paclitaxel, cisplatin, and 5-fluorouracil.2 Among these drugs, cisplatin is first approved as an antineoplastic agent, which is widely used in the treatment of diverse cancers.3 However, it has been uncovered that cisplatin causes drug resistance in chemotherapy, which seriously affects patients’ survival rates.4 It is reported that glycolysis is closely associated with drug resistance, and glycolysis suppression of cancer cells is a promising strategy for overcoming antimicrobial resistance.5,6 Convincing evidence has revealed that the uncontrollable proliferation of tumor cells is often accompanied by adaptive changes in energy metabolism.7 As early as the 1950s, Otto Warburg discovered that tumor cells have abnormalities in glycometabolism: even under normoxic conditions, tumor cells would reprogram their metabolic programs and preferentially select glycolytic pathways for energy.8 It is currently known that the sirtuin (sirt) family is primarily related to the modulation of metabolic diseases and aging and is widely involved in tumor progression.9 The sirtuin family is mainly composed of seven different members (sirt1–7), among which sirt1 is demonstrated to be implicated in chemotherapeutics resistance in cancers. 10 It participates in DNA damage and repair, and apoptosis and metabolism of drugs cause multi-drug resistance. 11 Moreover, sirt1 is unveiled to facilitate glycolysis, accelerating malignant progression in bladder cancer. 12 HK2 (hexokinase 2) is one of four isozymes of hexokinase in mammalian metabolism.13 The HK2 functions in tumor cells include metabolic rewiring toward aerobic glycolysis, autophagy tuning to handle nutrient shortages, and shielding from cell death stimuli.14 Especially, sirt1 is proven to positively regulate HK2 expression, contributing to glycolysis in the malignant progression ofTK6 cells.15 Nevertheless, whether sirt1 can interact with HK2 to affect glycolysis in ESCC has not been reported. Therefore, in this study, we hypothesized that the chemotherapeutic sensitivity of ESCC to cisplatin was regulated by sirt1, and the glycolysis pathway was related to this regulation. Several vivo and in vitro experiment

FAQs

What was the main goal of the study on sirtuin1 and cisplatin?

To evaluate how sirtuin1 (sirt1) affects the chemotherapeutic sensitivity of esophageal squamous cell carcinoma to cisplatin.

How did altering sirt1 expression affect ESCC sensitivity to cisplatin?

Sirt1 knockdown increased ESCC sensitivity to cisplatin, while sirt1 overexpression was observed in ESCC patients and cells.

What role does glycolysis play in cisplatin resistance according to the study?

Glycolysis was associated with ESCC chemotherapy resistance to cisplatin, and sirt1 modulated this process through HK2 to increase cisplatin chemosensitivity.

Sep 21, 2026

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