Treatment with β-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway

Xiaomeng, Fu; Lv, Lei; An, Jing; Jiang, Juan; Qi, Yue; Yuan, Dandan

doi:10.1590/1414-431x20208885

Cited by 17 publications

(10 citation statements)

References 39 publications

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“…The Reactome database 5 indicated that there were multiple signaling pathways of KLF6. Meanwhile, previous studies have shown that down-regulation of the NF-κB signaling pathway inhibits the growth of OC, and even highlighted as a potential therapeutic strategy against OC ( Xiaomeng et al, 2020 ). Therefore, we speculated that miR-630/KLF6 affected the EVs-induced CAF activation by regulating the NF-κB pathway.…”

Section: Resultsmentioning

confidence: 99%

Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

Cui

Wang

Xie

2021

Front. Cell Dev. Biol.

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Ovarian cancer (OC) is a lethal gynecological malignancy. Extracellular vesicles (EVs) are crucial media in cell-to-cell communication by carrying microRNAs (miRs). The current study aims to investigate the underlying mechanism of miR-630 carried by OC cell-derived EVs in regard to invasion and metastasis of OC cells. miRs related to OC metastasis were searched and screened. The expression patterns of screened miRs in human normal fibroblasts (NFs) and carcinoma-associated fibroblasts (CAFs) were detected using RT-qPCR. miR-630 related to OC metastasis and CAFs activation was analyzed further. The levels of FAP and α-SMA were detected using Western blotting and immunofluorescence. The migration of NFs was measured using Transwell assay. OC cell-derived EVs were isolated and identified. Uptake of EVs by NFs was observed using immunofluorescence staining. The culture supernatant of NFs was collected and used to culture the low metastasis cell line OVCAR8. The migration and invasion of OC cells and epithelial mesenchymal transition (EMT) were measured. Moreover, a xenograft model was established by injecting OVCAR8 cells of different groups into nude mice. Lastly, the effect of EV-pretreated NFs on invasion and metastasis of OC cells was observed in vivo. miR-630 was upregulated in OC cells and CAFs, and further associated with CAF activation and OC metastasis. miR-630 overexpression increased the levels of FAP and α-SMA in NFs, resulting in the transformation of NFs into CAFs. EVs carried miR-630 into NFs and EVs promoted CAF activation. miR-630 targeted KLF6. miR-630 inhibition or KLF6 overexpression attenuated EVs-induced CAF activation. EVs activated the NF-κB pathway via the miR-630/KLF6 axis. The conditioned medium of NFs pretreated with EVs promoted the invasion and metastasis of OVCAR8 cells, while downregulating miR-630 in EVs partially inhibited the promotive effect of NFs. EV-pretreated NFs promoted invasion and metastasis of OC in vivo. In conclusion, EVs carried miR-630 into NFs, thereby facilitating CAF activation and promoting invasion and metastasis of OC by inhibiting KLF6 and activating the NF-κB pathway. Our findings might offer a novel mechanism of invasion and metastasis of OC from the perspective of tumor microenvironment.

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Section: Resultsmentioning

confidence: 99%

Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

Cui

Wang

Xie

2021

Front. Cell Dev. Biol.

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“…Numerous studies (Ahn, Sethi, & Aggarwal, 2008;Dana, Vaseghi, & Haghjooy Javanmard, 2020;M. Deng, Dai, Yu, Tao, & Lung, 2020;Fu et al, 2020;Ghasemi et al, 2019;Khalil et al, 2020;Monisha et al, 2017;Morgan, Garg, Tergaonkar, Tan, & Sethi, 2020;Su, Ahmad, Zou, & Zou, 2020;Xiaomeng et al, 2020;Zou, Hu, & Jiang, 2020) have confirmed that NF-κB is a key regulator of stress and inflammation, participates in cell proliferation and apoptosis, and is important in signal transduction during tumorigenesis and progression. Oleuropein reduced the expression of nuclear factor-kappa Β (NF-κB) in different tumor models (Elamin et al, 2019;Giner et al, 2016;L.…”

Section: Nuclear Factor-kappa βmentioning

confidence: 99%

An updated review on the potential antineoplastic actions of oleuropein

Zheng

Liu

Xiao

et al. 2021

Phytotherapy Research

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It is a phenolic compound and the most luxuriant in olives. The detailed information related to the anticancer effects of oleuropein was collected from the internet database PubMed/Medline, ResearchGate, Web of Science, Wiley Online Library, and Cnki using appropriate keywords until the end of October 2021. Oleuropein has been shown to have antioxidant, anticancer, antiinflammatory, cardioprotective, neuroprotective, and hepatoprotective effects. Previous studies also revealed that oleuropein could effectively inhibit the malignant progression of esophageal cancer, gastric cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, ovarian cancer, prostate cancer, and cervical cancer. Recently, the role of oleuropein in inhibiting tumor cell proliferation, invasion, and migration and inducing tumor cell apoptosis has gained extensive attention. In this review, we have summarized the latest research progress related to the antioncogenic mechanisms and the potential role of oleuropein in targeting different human malignancies. Based on these findings, it can be concluded that oleuropein can function as a promising chemopreventive and chemotherapeutic agent against cancer, but its more detailed anticancer effects and underlying mechanisms need to be further validated in future preclinical as well as clinical studies.

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“…Studies have shown that PTX are able to induce apoptosis of tumor cells ( Zhao et al, 2019 ; Xiaomeng et al, 2020 ); therefore, we explored whether PTX could induce RA-FLS apoptosis using Annexin-FITC/PI staining. After treating RA-FLSs with 100 and 200 nM PTX for 24 and 48 h, apoptosis was examined by flow cytometry analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Apoptosis is widely accepted as a process of programmed cell death. Studies have shown that PTX and its agent can induce apoptosis of tumor cells, such as giant cells, sarcoma cells, lung cancer cells, breast cancer cells, and liver cancer cells ( Ren et al, 2018 ; Xiao et al, 2019 ; Li et al, 2020 ; Xiaomeng et al, 2020 ). Therefore, we investigated whether PTX induces FLS apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Paclitaxel (PTX), a compound extracted from Taxus, is often used in cancer owing to its remarkable antitumor efficacy ( Shetti et al, 2019 ; Xiaomeng et al, 2020 ; Zhang et al, 2020 ). Although PTX has been extensively studied in the field of oncology, researchers have found that PTX also exerts therapeutic effects on non-neoplastic diseases, such as inflammatory diseases, fibroproliferative diseases, and vascular diseases ( Zhang et al, 2010 ; Wang et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis

et al. 2021

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Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.

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Treatment with β-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway

Cited by 17 publications

References 39 publications

Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

An updated review on the potential antineoplastic actions of oleuropein

Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis

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