Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway

Tong, Xiaopei; Jiang, Pei; Li, Yao; Guo, Lin; Zhang, Huimin; Zhang, Bikui; Yan, Miao

doi:10.1248/cpb.c19-00300

Cited by 12 publications

(8 citation statements)

References 16 publications

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“…Akt is the central node of a large number of signaling pathways by signaling upstream regulatory proteins such as PTEN, PI3K, and receptor tyrosine kinases to many downstream effectors such as GSK-3β, FOXO, and MDM2 ( Revathidevi and Munirajan, 2019 ). Xie’s results showed that the expression of P-Akt and P-GSK-3β in A549/Taxol cell lines was significantly upregulated after triptolide treatment, which was also observed by Yang et al (2011) , Meng et al (2015 ), and Tong et al (2019) . Considering the specificity of Akt as the central node, this may partially explain the involvement of triptolide in NF-κB, p53, and Wnt/β-catenin signaling pathways in the regulation of NSCLC progression.…”

Section: Mechanism Of Triptolide On Non–small Cell Lung Cancermentioning

confidence: 87%

“…Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-Tkis) represented by gefitinib have shown good efficacy as adjuvant therapy for early NSCLC patients with EGFR-sensitized mutations ( Ye et al, 2021 ). Tong et al (2019) found by MTT analysis and combination index (CI) analysis that gefitinib, erlotinib, and icotinib had synergistic effects with triptolide at different concentrations (5 and 15 μm) on H1975 cell lines. However, there was no synergistic effect on the H1299 cell line.…”

Section: Potential Of Triptolide In Drug Combinationmentioning

confidence: 99%

“…Given the toxicity characteristics of triptolide in vitro and in vivo , some studies focused on the drug combination of triptolide. Low-dose triptolide can increase the sensitivity of NSCLC cells to chemotherapy with cisplatin and other drugs ( Zhu et al, 2018 ) and overcome the resistance of NSCLC cells to gefitinib and other drugs ( Tong et al, 2019 ; Li et al, 2020 ). This study systematically summarized the targets and molecular mechanisms of triptolide in NSCLC, and summarized the latest progress of triptolide combined therapy for NSCLC, as shown in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

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A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer

Qiu

Zhai

2022

Front. Pharmacol.

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In recent decades, natural products derived from plants and their derivatives have attracted great interest in the field of disease treatment. Triptolide is a tricyclic diterpene extracted from Tripterygium wilfordii, a traditional Chinese medicine, which has shown excellent therapeutic potential in the fields of immune inflammation and cancer treatment. In this study, 1,106 Web-of-Science-indexed manuscripts and 1,160 Chinese-National-Knowledge-Infrastructure-indexed manuscripts regarding triptolide published between 2011 and 2021 were analyzed, mapping the co-occurrence networks of keywords and clusters using CiteSpace software. The research frontier and development trend were determined by keyword frequency and cluster analysis, which can be used to predict the future research development of triptolide. Non–small cell lung cancer (NSCLC) is most common in lung cancer patients, accounting for about 80% of all lung cancer patients. New evidence suggests that triptolide effectively inhibits the development and metastasis of NSCLC by the induction of apoptosis, reversion of EMT, and regulation of gene expression. Specifically, it acts on NF-κB, MAPKs, P53, Wnt/β-catenin, and microRNAs (miRNAs), signaling pathways and molecular mechanisms. Consequently, this article reviews the research progress of the anti-NSCLC effect of triptolide. In addition, attenuated studies on triptolide and the potential of tumor immunotherapy are also discussed.

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Section: Mechanism Of Triptolide On Non–small Cell Lung Cancermentioning

confidence: 87%

Section: Potential Of Triptolide In Drug Combinationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer

Qiu

Zhai

2022

Front. Pharmacol.

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“…It is a small molecule compound with anti-tumor, anti-angiogenesis, anti-inflammatory and pro-apoptotic effects [8]. TP has anti-cancer effect against liver [9,10], ovarian [11][12][13][14], lung [15][16][17], gastric [18,19], breast [20,21].…”

Section: Introductionmentioning

confidence: 99%

Triptolide Inhibits the Biological Processes of HUVEC and HepG2 Cells via the Serine Palmitoyltransferase Long Chain Base Subunit 2/sphingosine-1-phosphate Signaling Pathway

Tan

Zhu

et al. 2021

Preprint

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Background: Hepatocellular carcinoma is a cancer that has a high incidence in men, and its incidence is increasing year by year. Studies show that angiogenesis plays an important role in the formation of tumors, not only providing nutrients to tumor cells, but also closely related to tumor growth and metastasis. So, how to find new anti-vascular and anti-tumor targets for the pathogenesis of liver cancer is a key issue that needs to be resolved.Methods: After treating Human umbilical vein endothelial cells (HUVEC) and HepG2 cells with different concentrations of triptolide (TP), the relationship between TP's anti-vascular and anti-tumor activities and sphingolipids was investigated respectively. Then, the three-dimensional co-culture model was used to explore the correlation between HUVEC and HepG2 cells, and to find the relationship between it and sphingolipids.Results: This study explored the effects of TP on the proliferation, migration, adhesion and tube formation of HUVEC cells, as well as the effects on the proliferation, migration and invasion of HepG2 cells. And through the PCR Array assay to screen the changes of related sphingolipid genes, it was found that serine palmitoyltransferase long chain base subunit 2 (SPTLC2) was most likely to be related to the effect of TP. In further transfection experiments, it was found that down-regulation of SPTLC2 can inhibit the proliferation, migration, adhesion and tube formation of HUVEC cells, and down-regulation of SPTLC2 can also inhibit the proliferation, migration and invasion of HepG2 cells. The up-regulation of SPTLC2 has opposite effects in these two cell lines. In the three-dimensional co-culture model of HUVEC and HepG2 cells, it was found for the first time that HUVEC cells can promote the biological process of HepG2 cells. It was found through enzyme linked immunosorbent assay (ELISA) and western blot experiments that it may be achieved through the sphingosine-1-phosphate (S1P)/S1P receptors (S1PRs) pathway. Finally, we found that the promotion effect of HUVEC cells on HepG2 cells was significantly inhibited after HUVEC cells were treated with TP.Conclusions: These data confirmed that the level of SPTLC2 may be related to the anti-vascular and anti-tumor effects of TP. The data also showed that there was a correlation between the viability of HepG2 cells and HUVEC cells, which may be related to the expression of S1P/S1PRS. Ultimately, these data may help discover new anti-tumor targets.

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“…It is a small molecule compound with anti-tumor, anti-angiogenesis, anti-inflammatory and pro-apoptotic effects [8]. TP has anti-liver cancer [9,10], ovarian cancer [11][12][13][14], lung cancer [15][16][17], gastric cancer [18,19], breast cancer [20,21] effects.…”

Section: Introductionmentioning

confidence: 99%

Triptolide Inhibited Liver Cancer Growth Based Through SPTLC2-S1P Signal Pathway

Tan

Zhu

et al. 2021

Preprint

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Background: Hepatocellular carcinoma is a cancer that has a high incidence in men, and its incidence is increasing year by year. Studies show that angiogenesis plays an important role in the formation of tumors, not only providing nutrients to tumor cells, but also closely related to tumor growth and metastasis. So, how to find new anti-vascular and anti-tumor targets for the pathogenesis of liver cancer is a key issue that needs to be resolved. Methods: After treating HUVEC and HepG2 cells with different concentrations of TP, the relationship between TP's anti-vascular and anti-tumor activities and sphingolipids was investigated respectively. Then, the three-dimensional co-culture model was used to explore the correlation between HUVEC and HepG2 cells, and to find the relationship between it and sphingolipids. Results: TP can inhibit the tube formation process of HUVEC cells. Through PCR Array, PCR and Western Blot experiments, it is found that it may achieve this effect by down-regulating SPTLC2. TP can also inhibit the proliferation, migration and invasion of HepG2 cells through the same mechanism. In the three-dimensional co-culture model of HUVEC and HepG2 cells, it was found for the first time that HUVEC can promote the biological process of HepG2 cells. It was found through ELISA and Western Blot experiments that it may be achieved through the S1P/S1PRS pathway, and TP was found in the dosing experiment. It can significantly inhibit the induction of HUVEC on HepG2 cells. Conclusions: These data confirm that the level of SPTLC2 may be related to the anti-vascular and anti-tumor effects of TP. The data also showed that there is a correlation between the viability of HepG2 cells and HUVEC cells, which may be related to the expression of S1P/S1PRS. Ultimately, these data may help discover new anti-tumor targets.

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Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway

Cited by 12 publications

References 16 publications

A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer

A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer

Triptolide Inhibits the Biological Processes of HUVEC and HepG2 Cells via the Serine Palmitoyltransferase Long Chain Base Subunit 2/sphingosine-1-phosphate Signaling Pathway

Triptolide Inhibited Liver Cancer Growth Based Through SPTLC2-S1P Signal Pathway

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