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Canagliflozin interrupts mTOR-mediated inflammatory signaling and attenuates DMBA-induced mammary cell carcinoma in rats
Biomedicine & Pharmacotherapy ( IF 7.5 ) Pub Date : 2022-09-15 , DOI: 10.1016/j.biopha.2022.113675
Marwa Sabaa 1 , Maha H Sharawy 1 , Mohamed El-Sherbiny 2 , Eman Said 3 , Hatem A Salem 1 , Tarek M Ibrahim 1
Affiliation  

Background

Breast cancer prevalence has been globally increasing, therefore, introducing novel interventions in cancer treatment is of a significant importance. The present study was designed to investigate the anti-cancer effect of Canagliflozin (CNG) in an experimental model of DMBA-induced mammary carcinoma in female rats.

Methods

18 female rats were divided into three experimental groups: Normal control, DMBA control, DMBA+ CNG treated group. DMBA (7.5 mg/kg) was injected subcutaneously in the mammary cells twice weekly for 4 weeks and CNG (10 mg/kg) was orally administered daily for an additional 3 weeks while DMBA control rats only received the vehicle for 3 weeks. Tumors’ weight and volume were measured, BRCA-1 and TAC were quantified in serum samples, mTOR, caspase-1, NFκB, IL-1β, NLRP3, GSDMD and MDA were quantified in tumors’ homogenates. Results: CNG treatment increased the BRCA-1 expression, suppressed mTOR inflammatory pathway, attenuated tumor inflammatory mediators; NLRP3, GSDMD, NFκB, IL-1β, suppressed the oxidative stress and inhibited tumor expression of the proliferation biomarker; Ki67.

Conclusion

CNG modulated mTOR-mediated signaling pathway and attenuated pyroptotic, inflammatory pathways, suppressed oxidative stress and eventually inhibited DMBA-induced mammary carcinoma proliferation.



中文翻译:

Canagliflozin 中断 mTOR 介导的炎症信号并减弱 DMBA 诱导的大鼠乳腺细胞癌

背景

乳腺癌患病率在全球范围内呈上升趋势,因此,在癌症治疗中引入新的干预措施非常重要。本研究旨在研究卡格列净 (CNG) 在 DMBA 诱导的雌性大鼠乳腺癌实验模型中的抗癌作用。

方法

18只雌性大鼠分为三个实验组:正常对照组、DMBA对照组、DMBA+CNG治疗组。DMBA (7.5 mg/kg) 每周两次在乳腺细胞中皮下注射,持续 4 周,并且 CNG (10 mg/kg) 每天口服施用另外 3 周,而 DMBA 对照大鼠仅接受载体 3 周。测量肿瘤的重量和体积,量化血清样品中的 BRCA-1 和 TAC,量化肿瘤匀浆中的 mTOR、caspase-1、NFκB、IL-1β、NLRP3、GSDMD 和 MDA。结果:CNG 治疗增加了 BRCA-1 的表达,抑制了 mTOR 炎症通路,减弱了肿瘤炎症介质;NLRP3、GSDMD、NFκB、IL-1β,抑制氧化应激,抑制肿瘤增殖生物标志物的表达;基67。

结论

CNG 调节 mTOR 介导的信号通路并减弱细胞焦亡、炎症通路,抑制氧化应激并最终抑制 DMBA 诱导的乳腺癌增殖。

更新日期:2022-09-15
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