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二甲双胍通过降低大鼠体内的转化生长因子β受体I-瞬时受体电位香草酸亚型1信号传导来缓解骨癌疼痛。

Metformin relieves bone cancer pain by reducing TGFβRI-TRPV1 signaling in rats.

作者信息

Zhou Fang, Qian He-Ya, Wang Ke, Gu Yong-Juan, Liu Pei-Lin, Zhang Ling, Chen Long, Song Yu, Chen Ya-Nan, Zhang Hai-Long

机构信息

Center for Translational Medicine, Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China.

Department of Pain, Suzhou Wuzhong People's Hospital, Suzhou 215128, China.

出版信息

Heliyon. 2024 Jul 20;10(15):e34991. doi: 10.1016/j.heliyon.2024.e34991. eCollection 2024 Aug 15.

DOI:10.1016/j.heliyon.2024.e34991
PMID:39157315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11328085/
Abstract

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFβ1 in the metastatic bone tissue, and raised the expression of TGFβRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFβRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFβ1, TGFβRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFβ1-TGFβRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

摘要

常见的癌症并发症包括骨癌疼痛（BCP），传统镇痛药对此缓解效果不佳。迫切需要更安全有效的治疗方法。二甲双胍可缓解骨关节炎疼痛，但二甲双胍对BCP的镇痛作用尚未得到充分研究。本研究旨在探讨二甲双胍在BCP大鼠中的镇痛作用及其分子机制。我们发现，将Walker 256细胞移植到胫骨骨髓腔会加重BCP大鼠的机械性异常性疼痛，增加转移骨组织中TGFβ1的表达，并提高BCP大鼠L4-6背根神经节（DRG）中TGFβRI和TRPV1的表达。而SD208选择性阻断TGFβRI可明显提高BCP大鼠的爪部退缩阈值（PWT），同时降低L4-6 DRG中TRPV1的表达。值得注意的是，持续给予二甲双胍治疗可降低TGFβ1、TGFβRI和TRPV1的表达，并长期缓解BCP大鼠的机械性异常性疼痛。总之，这些结果表明二甲双胍可改善骨癌疼痛，TGFβ1-TGFβRI-TRPV1的下调可能是二甲双胍介导的BCP镇痛作用的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/6cd4ebae2bc6/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/7042d3902277/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/cf343f874458/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/4db7d6ab6d2e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/6401103506a4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/66782fef65e2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/9ab291d360d4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/abd537b454d6/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/4c61c7f3302f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/6cd4ebae2bc6/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/7042d3902277/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/cf343f874458/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/4db7d6ab6d2e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/6401103506a4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/66782fef65e2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/9ab291d360d4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/abd537b454d6/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/4c61c7f3302f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4d/11328085/6cd4ebae2bc6/gr9.jpg

相似文献

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Metformin relieves bone cancer pain by reducing TGFβRI-TRPV1 signaling in rats.

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[3]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Mechanisms of Cancer-Induced Bone Pain.

J Pain Res. 2025-1-20

本文引用的文献

[1]
The Presence of TGFβ3 in Human Ovarian Intrafollicular Fluid and Its Involvement in Thromboxane Generation in Follicular Granulosa Cells through a Canonical TGFβRI, Smad2/3 Signaling Pathway and COX-2 Induction.

Int J Mol Sci. 2024-5-20

[2]
Serum-Induced Proliferation of Human Cardiac Stem Cells Is Modulated via TGFβRI/II and SMAD2/3.

Int J Mol Sci. 2024-1-12

[3]
[Metformin alleviates pathologic pain in mice with radiation dermatitis by inhibiting p38MAPK/NF-κB signaling pathway].

Nan Fang Yi Ke Da Xue Xue Bao. 2023-10-20

[4]
Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex.

Transl Psychiatry. 2023-10-11

[5]
Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.

Mol Psychiatry. 2023-9

[6]
Metformin and curcumin co-encapsulated chitosan/alginate nanoparticles as effective oral carriers against pain-like behaviors in mice.

Int J Pharm. 2023-6-10

[7]
Metformin: update on mechanisms of action and repurposing potential.

Nat Rev Endocrinol. 2023-8

[8]
Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway.

Metab Brain Dis. 2023-8

[9]
The modifier effect of physical activity, body mass index, and age on the association of metformin and chronic back pain: A cross-sectional analysis of 21,899 participants from the UK Biobank.

PLoS One. 2023

[10]
Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages.

Cells. 2022-12-16

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