Notoginsenoside R1 counteracts mesenchymal stem cell-evoked oncogenesis and doxorubicin resistance in osteosarcoma cells by blocking IL-6 secretion-induced JAK2/STAT3 signaling

Lu, Minan; Xie, Keqin; Lu, Xianzhe; Lu, Lu; Yu, Shichong; Tang, Yue

doi:10.1007/s10637-020-01027-9

Cited by 21 publications

(11 citation statements)

References 34 publications

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“…After its discovery, DOX was considered as the first option in treatment of cancer patients and showed promising clinical results. However, these ideal findings disappeared with development of DOX resistance [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

et al. 2021

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Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

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Section: Introductionmentioning

confidence: 99%

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

et al. 2021

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“…With the accumulation of reports about the cross‐talk between MSCs and tumor cells, the role of MSCs in tumor development is contradictory, and MSC‐based cellular therapy in tumors is still controversial 42,43 . However, a large number of studies have reported the pro‐tumor effects of IL‐6 secreted by MSCs in lung cancer, 15 lymphoma, 44 breast cancer, 45 osteosarcoma, 46 and colorectal cancer 47 . At present, agents targeting IL‐6, JAKs, or STATs are in preclinical and clinical investigations; the JAK inhibitor, ruxolitinib has been approved for the treatment of myelofibrosis and polycythemia vera 48 .…”

Section: Discussionmentioning

confidence: 99%

Acute myeloid leukemia (AML)‐derived mesenchymal stem cells induce chemoresistance and epithelial–mesenchymal transition‐like program in AML through IL‐6/JAK2/STAT3 signaling

Dong

Zhang

et al. 2023

Cancer Science

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Acute myeloid leukemia (AML) has a high rate of treatment failure due to increased prevalence of therapy resistance. Mesenchymal stem cells (MSCs) in the leukemia microenvironment contribute to chemoresistance in AML, but the specific mechanism remains unclear. The critical role of the epithelial-mesenchymal transition (EMT)-like profile in AML chemoresistance has been gradually recognized. However, there is no research to suggest that the AML-derived bone marrow mesenchymal stem cells

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“…143B [89] Isoquercitrin Bidens pilosa L. 143B, U2OS [90] Polydatin Reynoutria japonica Houtt. MG-63, Saos-2 [91] Curcumin Curcuma longa L. U2OS [92] Baicalein Rhizoma coptidis 143B, MG-63, U2OS [93] Allicin Allium sativum Saos-2, U2OS [94] Cantharidin Mylabris phalerata Pallas U2OS, 143B, Saos-2, MG-63, MNNG [95] Cinnamaldehyde Cinnamomum cassia Presl 143B, U2OS, Saos-2, MG-63, HEB, HS5, LO2 [96] Lycorine Lyco salvia miltiorrhiza 143B, MG-63, Saos-2, U2OS [97] JAK/STAT3 pathway Notoginsenoside R1 Panax notoginseng U2OS, MG-63 [98] Polydatin Reynoutria japonica Houtt.…”

Section: Signaling Pathwaymentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of “multiple targets and multiple pathways,” and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/β-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-β (TGF-β)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

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Notoginsenoside R1 counteracts mesenchymal stem cell-evoked oncogenesis and doxorubicin resistance in osteosarcoma cells by blocking IL-6 secretion-induced JAK2/STAT3 signaling

Cited by 21 publications

References 34 publications

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

Acute myeloid leukemia (AML)‐derived mesenchymal stem cells induce chemoresistance and epithelial–mesenchymal transition‐like program in AML through IL‐6/JAK2/STAT3 signaling

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

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