Celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting ERK1/2 and SMAD2/3 phosphorylation

Li, Fengfeng; Fan, Cunyi; Zeng, Bingfang; Zhang, Changqing; Chai, Yimin; Liu, Shen; Ouyang, Yuanming

doi:10.3892/mmr.2011.722

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…It is known that Cox-2 inhibition can affect the proliferative state of fibroblasts in vitro [33]. Therefore, we hypothesized that ASA treatment could influence numbers of tumor-infiltrating CAFs in principle.…”

Section: Resultsmentioning

confidence: 99%

Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs

et al. 2015

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Anti-angiogenic therapies were approved for different cancers. However, significant primary and secondary resistance hampers efficacy in several tumor types including breast cancer. Thus, we need to develop clinically applicable strategies to enhance efficacy of anti-angiogenic drugs.We report that anti-angiogenic therapies can induce upregulation of cyclooxygenase-2 (Cox-2) and of its product prostaglandin E2 (PGE2) in breast cancer models. Upon Cox-2 inhibition PGE2 levels were normalized and efficacy of anti-vascular endothelial growth factor receptor 2 (anti-VEGFR-2) antibodies and sunitinib was enhanced. Interestingly, both treatments exerted additive anti-angiogenic effects. Following Cox-2 inhibition, we observed reduced infiltration of tumors with cancer-associated fibroblasts (CAFs) and lower levels of pro-angiogenic factors active besides the VEGF axis including hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2). Mechanistic studies indicated that Cox-2 inhibition reduced PGE2-induced migration and proliferation of CAFs via inhibiting phosphorylation of Akt.Hence, Cox-2 inhibition can increase efficacy of anti-angiogenic treatments and our findings might pave the road for clinical investigations of concomitant blockade of Cox-2 and VEGF-signaling.

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Section: Resultsmentioning

confidence: 99%

Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs

et al. 2015

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“…TGF-β1 induced phosphorylation of Smad3 and increased Col3 expression, which can be prevented by Smad3 depletion (30). Previous studies have strongly indicated that Erk1/2 plays a synergistic role in Smad-mediated collagen synthesis, as initiated by TGF-β1 in some cells of fibrotic diseases such as human dermal fibroblasts and myofibroblasts (31, 32). However, it is not well known what roles Erk1/2 play in activating Smad3.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts

Pang

Wang

et al. 2019

BMB Rep.

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Keloids are the most common pathological form of trauma healing, with features that seriously affect appearance and body function, are difficult to treat and have a high recurrence rate. Emerging evidence suggests that miRNAs are involved in a variety of pathological processes and play an important role in the process of fibrosis. In this study, we investigated the function and regulatory network of miR-152-5p in keloids. The miRNA miR-152-5p is frequently downregulated in keloid tissue and primary cells compared to normal skin tissue and fibroblasts. In addition, the downregulation of miR-152-5p is significantly associated with the proliferation, migration and apoptosis of keloid cells. Overexpression of miR-152-5p significantly inhibits the progression of fibrosis in keloids. Smad3 is a direct target of miR-152-5p, and knockdown of Smad3 also inhibits fibrosis progression, consistent with the overexpression of miR-152-5p. The interaction between miR-152-5p and Smad3 occurs through the Erk1/2 and Akt pathways and regulates collagen3 production. In summary, our study demonstrates that miR-152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a potential therapeutic target of keloids.

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