Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells

Li, Fangqiong; Cui, Huaizhong; Jin, Xin; Gong, Xiaoting; Wang, Wei; Wang, Juan

doi:10.3892/or.2020.7542

Cited by 14 publications

(14 citation statements)

References 44 publications

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“…Recently, some scholars also studied the phenotype of EMT in glioma and found that, as the activators of EMT, ZEB1 and ZEB2 of the SNAIL family can, to varying degrees, promote the invasion of GBM in vivo and in vitro (10,11). TP causes changes in EMT-like phenotypes that are closely related to tumor invasion and metastasis, as reported in pancreatic cancer (12,13), lung cancer (14,15), and colon cancer (16). However, whether or not TP causes changes in the EMT of glioma cells is still unknown.…”

Section: Introductionmentioning

confidence: 93%

Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy

Lai¹,

Liu²,

Zhu³

et al. 2021

Ann Transl Med

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Background: To observe the effects of triptolide (TP) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of glioma cells, and to explore the possible mechanisms of phenotypic changes in EMT.Methods: The U87 and U251 glioma cell lines were treated TP. The Cell Counting Kit-8 (CCK-8) method was used to detect the half-maximal inhibitory concentration (IC 50 ) of TP in these two cell lines and the inhibition of cell proliferation at the IC 50 concentration. The wound-healing experiment and Transwell invasion assay were used to detect the cells' migration and invasion abilities, respectively. Using western blot protocol, the expression levels of the EMT markers were analyzed, and the levels of the autophagy markers were also detected. The pEGFP-C2-LC3B plasmid was transfected into glioma cells, and the effect of TP on autophagy was detected by immunofluorescence. A subcutaneous tumor model in nude mice was established to observe the effect of TP on cell proliferation in vivo, and immunohistochemistry (IHC) was used to detect the expression levels of EMT markers in mouse tumor tissues.Results: TP significantly inhibited the proliferation of U87 and U251 cells in a dose-and time-dependent manner. TP had a significant inhibitory effect on the migration and invasion of U87 and U251 cells. Western blot showed that TP reversed the process of EMT in glioma cells, which was evidenced by the upregulated expression of the epithelial marker E-cadherin, and the downregulated expression of the mesenchymal markers N-cadherin, Vimentin, ZEB1, Snail, and Slug. TP increased autophagy in glioma cells, increased the LC3B II/I ratio, and upregulated Beclin-1 and Atg-7 expression. Immunofluorescence showed that the number of autophagosomes increased significantly after TP was applied to cells. In the nude mouse subcutaneous tumor model, experiments revealed an inhibitory effect of TP on glioma cell proliferation in vivo. IHC confirmed that the expression of E-cadherin was upregulated in mouse tumor tissues, while the expression levels of N-Cadherin and Vimentin were downregulated.Conclusions: TP can inhibit glioma cell proliferation, migration, and invasion, and reverse EMT progression. The possible mechanism of EMT reversal in glioma cells is that TP induces autophagy.

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Section: Introductionmentioning

confidence: 93%

Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy

Lai¹,

Liu²,

Zhu³

et al. 2021

Ann Transl Med

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“…Triptolide, a diterpene triepoxide that is a major bioactive natural compound isolated from Tripterygium wilfordii Hook.f. [Celastraceae], which is well known for its antiinflammatory effect (Noel et al, 2019;Li et al, 2020). Recently, triptolide has been demonstrated as a potential anti-tumor agent in pharmacological research regarding CRC therapy.…”

Section: Triptolidementioning

confidence: 99%

Traditional Chinese Medicines as Effective Reversals of Epithelial-Mesenchymal Transition Induced-Metastasis of Colorectal Cancer: Molecular Targets and Mechanisms

Chen

et al. 2022

Front. Pharmacol.

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Colorectal cancer (CRC) is the third most common type of cancer worldwide. Distant metastasis is the major cause of cancer-related mortality in patients with CRC. Epithelial-mesenchymal transition (EMT) is a critical process triggered during tumor metastasis, which is also the main impetus and the essential access within this duration. Therefore, targeting EMT-related molecular pathways has been considered a novel strategy to explore effective therapeutic agents against metastatic CRC. Traditional Chinese medicines (TCMs) with unique properties multi-target and multi-link that exert their therapeutic efficacies holistically, which could inhibit the invasion and metastasis ability of CRC cells via inhibiting the EMT process by down-regulating transforming growth factor-β (TGF-β)/Smads, PI3K/Akt, NF-κB, Wnt/β-catenin, and Notch signaling pathways. The objective of this review is to summarize and assess the anti-metastatic effect of TCM-originated bioactive compounds and Chinese medicine formulas by mediating EMT-associated signaling pathways in CRC therapy, providing a foundation for further research on the exact mechanisms of action through which TCMs affect EMT transform in CRC.

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“…Triptolide is a potent anti-tumor agent that has demonstrated inhibitory effect on cancer progression via targeting molecular pathways. Triptolide administration impairs the metastasis of lung cancer cells via EMT inhibition and reducing the expression levels of matrix metalloproteinase-9 (MMP9) [ 314 ]. This plant-derived natural compound induces apoptosis in lung cancer cells via miRNA-204-5p upregulation and the subsequent inhibition of Akt signaling [ 315 ].…”

Section: Microrna and Pten Relationshipmentioning

confidence: 99%

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

et al. 2021

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MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size of 19–24 nucleotides and a single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors in cancer via regulating molecular pathways. Breast and lung cancers are two malignant thoracic tumors in which the abnormal expression of miRNAs plays a significant role in their development. Phosphatase and tensin homolog (PTEN) is a tumor-suppressor factor that is capable of suppressing the growth, viability, and metastasis of cancer cells via downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation occurs in lung and breast cancers to promote PI3K/Akt expression, leading to uncontrolled proliferation, metastasis, and their resistance to chemotherapy and radiotherapy. miRNAs as upstream mediators of PTEN can dually induce/inhibit PTEN signaling in affecting the malignant behavior of lung and breast cancer cells. Furthermore, long non-coding RNAs and circular RNAs can regulate the miRNA/PTEN axis in lung and breast cancer cells. It seems that anti-tumor compounds such as baicalein, propofol, and curcumin can induce PTEN upregulation by affecting miRNAs in suppressing breast and lung cancer progression. These topics are discussed in the current review with a focus on molecular pathways.

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Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells

Cited by 14 publications

References 44 publications

Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy

Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy

Traditional Chinese Medicines as Effective Reversals of Epithelial-Mesenchymal Transition Induced-Metastasis of Colorectal Cancer: Molecular Targets and Mechanisms

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

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