The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

Ji, Liyan; Liu, Xi; Zhang, Shuwei; Tang, Shunan; Yang, Simin; Li, Shasha; Qi, Xiaoxiao; Yu, Siwang; Lu, Linlin; Meng, Xiangbao; Liu, Zhongqiu

doi:10.3390/molecules22111822

Cited by 20 publications

(11 citation statements)

References 42 publications

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“…The same applies for rofecoxib (Figure ), which showed to downregulate mRNA and protein levels of MRP1, but also GST, at a concentration of 10 μM using BGC‐823 gastric cancer cells . Here, it is worth to mention that downregulation of MRP1 transcript and protein has also been observed for other pharmacological and experimental drugs, such as fidarestat, LSS‐11, pantoprazole, and U0126 (Figure ) …”

Section: Pharmacological and Experimental Drugs And Synthetic Analogssupporting

confidence: 55%

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Stefan

Wiese

2018

Medicinal Research Reviews

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Multidrug resistance-associated protein 1 (MRP1, ABCC1) is an ATP-binding cassette (ABC) transport protein. This efflux pump uses the energy of ATP hydrolysis to export structurally diverse antineoplastic agents in human cancers. The upregulation of MRP1 (either inherent or acquired) is one major reason for the occurrence of the phenomenon called multidrug resistance (MDR). MDR is characterized by a reduced outcome of chemotherapy due to the active intracellular clearance of cytostatic drugs below the necessary effect concentration. Much effort has been made to overcome MDR, which implied high-throughput screenings of already known pharmacological and natural compounds, modification of intrinsic substrates, as well as design and synthesis of new inhibitors. This review is meant not only to summarize the most recent results over the past 10 years, but also to highlight major achievements regarding reversal of MRP1-mediated MDR, from the time of its discovery until today. The focus lies on small-molecule compounds that feature either direct MRP1 inhibition/transport blockage, toxicity against MRP1-overexpressing cells, inhibition/modification of intracellular processes necessary for MRP1 function, or modification of MRP1-related metabolic and genomic mechanisms. Considering all aspects, this review might be useful to (re)consider possible strategies to overcome MRP1-mediated MDR. Furthermore, it may be the basis for developing new, even better, highly potent, less toxic, and selective (as well as broad-spectrum) MRP1 inhibitors that will enter clinical evaluations in different malignancies and finally conduce to overcome MDR in general.

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Section: Pharmacological and Experimental Drugs And Synthetic Analogssupporting

confidence: 55%

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Stefan

Wiese

2018

Medicinal Research Reviews

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“…Regarding the interplay between STAT3, its target genes and MDR1, Ji et al 32 showed that a novel triazolonaphthalimide derivative LSS-11 could hinder the binding of STAT3 to the MDR1 and MRP1 promoters by conducting chromatin coimmunoprecipitation (ChIP) assay. Indicating MDR1 is regulated by the STAT3 at the transcription level.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A

Wang

Zuo

et al. 2019

Int. J. Biol. Sci.

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Osteosarcoma (OS) is the most common primary bone malignancy in adolescents. One major obstacle for current OS treatment is drug-resistance. Raddeanin A (RA), an oleanane-type triterpenoid saponin, exerts anti-tumor effects in several tumor models, but the effect of RA in human drug-resistant OS remained to be elucidated. In the present study, we investigated the anti-tumor effects of RA in both drug-sensitive and drug-resistant OS cells and its underlying mechanism. RA inhibited cell proliferation and colony formation and induced apoptotic cell death in a dose-dependent manner in both drug-sensitive and drug-resistant cells. Moreover, RA exposure resulted in the inhibition of interleukin-6 (IL-6)-induced JAK2/STAT3 signaling pathway activation and target gene expression in both drug-sensitive and drug-resistant cells. Meanwhile, we observed significantly increased MDR1 and STAT3 expression in drug-resistant OS cells compared with parental cells. STAT3 overexpression promoted chemo-resistance and MDR1 protein expression in both drug-sensitive OS cells and drug-resistant OS cells, while inhibiting STAT3 with siRNA sensitized OS cells to doxorubicin treatment. In addition, RA synergistically increased doxorubicin toxicity by increasing its cellular uptake, ablating efflux and downregulating MDR1 in drug-resistant cells with attenuation of STAT3 Phosphorylation. Finally, RA suppressed in vivo tumor growth and induced apoptosis in nude mouse using drug-resistant OS tibia orthotopic model. Taken together, RA is a promising potential therapeutic for the treatment of doxorubicin resistance in OS.

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“…For example, lncRNA LINC00460 promotes EGFR expression by downregulating miR-769-5p, which results in the resistance of NSCLC cells to gefitinib ( 220 ). LncRNA MALAT1 upregulates multiple drug resistance-related protein (MDR1) and multidrug resistance protein (MDR1) by inducing STAT3 phosphorylation, which eventually enhance the resistance of lung cancer cells to treatment with cisplatin ( 221 , 222 ). Though there is no specific clinical trial targeting lung cancer, it’s still a potential therapy for the comprehensive treatment of lung cancer.…”

Section: Current and Next Generation Therapiesmentioning

confidence: 99%

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value

et al. 2021

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Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In this review, we summarize the findings of recent clinical research studies on biomarkers detected in samples obtained from patients with lung cancer bone metastasis. These markers include the following: (1) bone resorption-associated markers, such as N-terminal telopeptide (NTx)/C-terminal telopeptide (CTx), C-terminal telopeptide of type I collagen (CTx-I), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), pyridinoline (PYD), and parathyroid hormone related peptide (PTHrP); (2) bone formation-associated markers, including total serum alkaline phosphatase (ALP)/bone specific alkaline phosphatase(BAP), osteopontin (OP), osteocalcin (OS), amino-terminal extension propeptide of type I procollagen/carboxy-terminal extension propeptide of type I procollagen (PICP/PINP); (3) signaling markers, including epidermal growth factor receptor/Kirsten rat sarcoma/anaplastic lymphoma kinase (EGFR/KRAS/ALK), receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB/osteoprotegerin (RANKL/RANK/OPG), C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4), complement component 5a receptor (C5AR); and (4) other potential markers, such as calcium sensing receptor (CASR), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), cytokeratin 19 fragment/carcinoembryonic antigen (CYFRA/CEA), tissue factor, cell-free DNA, long non-coding RNA, and microRNA. The prognostic value of these markers is also investigated. Furthermore, we listed some clinical trials targeting hotspot biomarkers in advanced lung cancer referring for their therapeutic effects.

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The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

Cited by 20 publications

References 42 publications

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value

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