Cisplatin induces chemoresistance through the PTGS2-mediated anti-apoptosis in gastric cancer

Lin, Xiaomian; Li, Song; Zhou, Chao; Li, Rong-zhen; Wang, Heng; Luo, Wenqiang; Huang, Yishan; Chen, Liankuai; Cai, Jialong; Wang, Tianxiang; Zhang, Qi-Hao; Cao, Hong; Wu, Xiaoping

doi:10.1016/j.biocel.2019.105610

Cited by 30 publications

(16 citation statements)

References 41 publications

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“…It has been reported that the expressions of antiapoptotic BCL2 and prostaglandin-endoperoxide synthase 2 (PTGS2) genes are abundant in gastric cancer and related to poor patient survival and are closely related to cisplatin resistance. Further research shows that PTGS2 participates in the development of cisplatin resistance by mediating the inhibitory effect of cisplatin on BCL2 expression [31]. In gastric cancer resistance studies, it was found that the combination of 6-ginger oil and cisplatin inhibited cell viability and enhanced cell cycle arrest in the G1 phase compared with cisplatin alone.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology‐Based Study on the Active Component and Mechanism of the Anti-Gastric-Cancer Effect of Herba Sarcandrae

Han

2021

Journal of Healthcare Engineering

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Background. Herba Sarcandrae is used in the clinical practice of traditional Chinese medicine to deal with gastric cancer. However, there are few studies on its precise mechanism. Method. In this study, a network pharmacological approach was utilized to construct a molecular/target/pathway molecular regulatory network for the anti-gastric-cancer effect of Herba Sarcandrae. The active components of Herba Sarcandrae and their potential mechanisms were explored. Chemical components of the Herba Sarcandrae were identified through a database, and they were evaluated and screened based on oral bioavailability and drug similarity. Results. Genes related to gastric cancer were found in the Gene Expression Omnibus (GEO) database, and gene targets related to anti-gastric-cancer were chosen by comparison. Using annotation, visualization, and a comprehensive discovery database, the function and related pathways of target genes were analyzed and screened. Cytoscape software was utilized to construct a component/target/pathway network for the antitumor effect of Herba Sarcandrae. Finally, 6 drug ingredients and 29 target genes related to gastric cancer were detected. IL-17 signaling pathway, NF-kappa B signaling pathway, and other signaling pathways were significantly enriched. Many signaling pathways that directly act on tumors and indirect pathways inhibit the development of gastric cancer. Conclusion. This study provides a scientific basis for further elucidating the mechanism of the anti-gastric-cancer effect of Herba Sarcandrae.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology‐Based Study on the Active Component and Mechanism of the Anti-Gastric-Cancer Effect of Herba Sarcandrae

Han

2021

Journal of Healthcare Engineering

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“…In gastric cancer cells, PRDX2 in cooperation with NF-kB-p65 subunit diminish ROS levels to suppress DNA damage and cell death, leading to CP resistance [156]. It seems that ROS participate in mechanisms that suppress CP-mediated apoptosis and mediate chemoresistance [157].…”

Section: Cisplatin Resistancementioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

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The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

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“…In a model of oxaliplatin-resistant colon cancer, EP4 blockade with L161982 inhibited CSC markers and tumorsphere formation (Huang et al, 2019). Likewise, cisplatin-resistant gastric cancer cells are sensitized to cisplatin via the suppression of COX-2/EP4/ERK1/2/P38 signaling by L161982 (Lin et al, 2019).…”

Section: Cancer Stem Cells and Ep4 In Chemoresistancementioning

confidence: 99%

Eicosanoids in Cancer: Prostaglandin E2 Receptor 4 in Cancer Therapeutics and Immunotherapy

2020

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The cyclooxygenase-2 (COX-2) enzyme is frequently overexpressed in epithelial malignancies including those of the breast, prostate, lung, kidney, ovary, and liver and elevated expression is associated with worse outcomes. COX-2 catalyzes the metabolism of arachidonic acid to prostaglandins. The COX-2 product prostaglandin E 2 (PGE 2) binds to four G-protein-coupled EP receptors designated EP1-EP4. EP4 is commonly upregulated in cancer and supports cell proliferation, migration, invasion, and metastasis through activation of multiple signaling pathways including ERK, cAMP/PKA, PI3K/AKT, and NF-kB. EP4 antagonists inhibit metastasis in preclinical models. Cancer stem cells, that underlie therapy resistance and disease relapse, are driven by the expression of EP4. Resistance to several chemotherapies is reversed in the presence of EP4 antagonists. In addition to tumor cell-autonomous roles of EP4, many EP4-positive host cells play a role in tumor behavior. Endothelial cell-EP4 supports tumor angiogenesis and lymphangiogenesis. Natural Killer (NK) cells are critical to the mechanism by which systemically administered EP4 antagonists inhibit metastasis. PGE 2 acts on EP4 expressed on the NK cell to inhibit tumor target cell killing, cytokine production, and chemotactic activity. Myeloid-derived suppressor cells (MDSCs), that inhibit the development of cytotoxic T cells, are induced by PGE 2 acting on myeloid-expressed EP2 and EP4 receptors. Inhibition of MDSC-EP4 leads to maturation of effector T cells and suppresses the induction of T regulatory cells. A number of EP4 antagonists have proven useful in dissecting these mechanisms. There is growing evidence that EP4 antagonism, particularly in combination with either chemotherapy, endocrine therapy, or immunebased therapies, should be investigated further as a promising novel approach to cancer therapy. Several EP4 antagonists have now progressed to early phase clinical trials and we eagerly await the results of those studies.

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Cisplatin induces chemoresistance through the PTGS2-mediated anti-apoptosis in gastric cancer

Cited by 30 publications

References 41 publications

Network Pharmacology‐Based Study on the Active Component and Mechanism of the Anti-Gastric-Cancer Effect of Herba Sarcandrae

Network Pharmacology‐Based Study on the Active Component and Mechanism of the Anti-Gastric-Cancer Effect of Herba Sarcandrae

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

Eicosanoids in Cancer: Prostaglandin E2 Receptor 4 in Cancer Therapeutics and Immunotherapy

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