Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Lyu, Yaqi; Xiao, Qingqing; Yin, Lifang; Yang, Lei; He, Wei

doi:10.1038/s41392-019-0054-9

Cited by 59 publications

(49 citation statements)

References 31 publications

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“…Integrins are adhesive receptors located on the cell surface, which mediate cell adhesion (32). Furthermore, MMPs induce cancer cell migration via degradation of the extracellular matrix (33). In the present study, costunolide dose-dependently downregulated the mRNA expression levels of integrins α2 and β1, as well as MMP2 in H1299 cells, which indicated the inhibitory potential of costunolide against NSCLC metastasis.…”

Section: Discussionsupporting

confidence: 62%

Costunolide induces apoptosis and inhibits migration and invasion in H1299 lung cancer cells

Wei

Qiu

et al. 2020

Oncol Rep

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Costunolide being a sesquiterpene lactone, is known to have anticancer properties. The present study investigated the anticancer effects of costunolide against the H1299 human non-small-cell lung cancer (NSCLC) cell line. Inhibition of cell viability by costunolide was assessed via a MTT assay. Furthermore, the apoptotic rate was detected using Annexin V/propidium iodide labeling. A colony forming cell assay was performed to investigate the antiproliferative effects of costunolide. Wound healing and Transwell assays were performed to determine the inhibitory effects of costunolide on migration and invasion, respectively. Western blot analysis was undertaken to determine protein expression, and reverse transcription-quantitative PCR was performed to assess mRNA expression levels. The results demonstrated that costunolide inhibited the viability of H1299 cells, with a half maximal inhibitory concentration value of 23.93±1.67 µM and induced cellular apoptosis in a dose-dependent manner. Furthermore, the colony formation, migrative and invasive abilities of the H1299 cells were inhibited in a dose-or time-dependent manner. The protein expression levels of E-cadherin increased and those of N-cadherin decreased following treatment with costunolide, which suggested that costunolide inhibited epithelial-to-mesenchymal transition. The mRNA levels of B-Raf, E-cadherin, N-cadherin, integrins α2 and β1, as well as matrix metalloproteinases 2 were also found to be regulated costunolide. These findings indicate the potential of costunolide in the treatment of NSCLC.

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Section: Discussionsupporting

confidence: 62%

Costunolide induces apoptosis and inhibits migration and invasion in H1299 lung cancer cells

Wei

Qiu

et al. 2020

Oncol Rep

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“…IL6 has been demonstrated to be involved in the development, progression and metastasis in several cancers (Huang et al, 2018). Matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis (Lyu, Xiao, Yin, Yang & He, 2019). We found that the expression levels of MMP9 and IL6 were decreased in thrombin deficient cells, and the expression of MMP9 and IL6 could be restored by adding exogenous thrombin (supplementary Fig.…”

Section: Resultsmentioning

confidence: 86%

A novel oncotherapy strategy, direct thrombin inhibitors suppress progression, dissemination and spontaneous metastasis in non-small cell lung cancer

Zhao

et al. 2020

Preprint

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Background and Purpose: Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in NSCLC primary tumor tissues and the association between prognosis of NSCLC patients remain largely unknown. Experimental Approach: Clinical pathological analysis was performed to determine the relationship between thrombin and tumor progression. Effect of r-hirudin and DTIP on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r-hirudin and DTIP. Therapeutic effect of combination of DTIP and chemotherapy was determined. Key Results: We illustrated thrombin expression in NSCLC tissues is closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumor progression. The novel thrombin inhibitors, r-hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumor growth and metastasis in orthotopic lung cancer model; inhibited cells invasion and prolonged survival after injection tumor cells via tail vein; they also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumors. The promotional activity of thrombin in invasion and metastasis was abolished in PAR-1 deficient-NSCLC cells. r-hirudin and DTIP inhibit tumor progression through the thrombin-PAR-1-mediated RhoA and NF-κB signaling cascades via inhibiting the MMP9 and IL6 expression. DTIP potentiated chemotherapy-induced growth and metastatic inhibition and inhibited chemotherapy-induced resistance in mice. Conclusions and Implications: Thrombin makes a substantial contribution, together with PAR-1, to NSCLC malignancy. We concluded the anticoagulants, r-hirudin and DTIP, could be expanded for anti-tumor therap. Combination therapy of DTIP and chemotherapy might achieve a better therapeutic effect.

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“…Besides the cancer cell-cell adhension, it also needs the ability to destroy the histological barrier of cancer cell invasion. Matrix metallopeptidase (MMP) is considered as an important member of the invasive process, which cancer cell secreted to dissolve the components of ECM or basement membrane [31]. It was previously reported that pristimerin down-regulated MMP2 and matrix metallopeptidase 9 (MMP9) to inhibit migration and invasion of esophageal squamous cell carcinoma (ESCC) [32].…”

Section: Discussionmentioning

confidence: 99%

Pristimerin induces apoptosis and inhibits proliferation, migration in H1299 Lung Cancer Cells

Guo

Lei

et al. 2020

J. Cancer

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Background: The natural occurring pristimerin, a quinonemethide triterpenoid, is extracted from a variety of species of the Celastraceae and Hippocrateaceae family. This research investigated the in vitro anti-cancer potential of pristimerin on NSCLC cells NCI-H1299 and elucidated the molecular mechanism. Methods: Cell growth inhibition by pristimerin was assessed using the MTT assay. Apoptosis was detected using the Annexin V/propidium iodide (PI) test. The colony forming assay was used to investigate the anti-proliferative effects of pristimerin. Wound healing assay and the transwell cell migration assay were utilized to determine the inhibitory effects of migration and invasion, respectively. Western blot was used to detect the protein expression, and real-time-quantitative (RT-q) PCR was used to analyze the mRNA expression. Results: The results showed that pristimerin inhibited the proliferation of H1299 cells with an IC50 value of 2.2 ± 0.34 µM and induced apoptosis in a dose-dependent manner. The colony formation ability was reduced in a dose-dependent manner. A marked inhibition of migration and invasion against H1299 cells was observed in a dose-or time-dependent manner. Moreover, the decreased protein levels of vimentin, F-actin, integrin β1, matrix metalloproteinase (MMP2) and Snail revealed the potential inhibition of epithelial-to-mesenchymal transition (EMT). The regulated mRNA levels of integrin β1, MMP2 and Snail indicated the great potential in the treatment of NSCLC. Conclusion: In conclusion, our study demonstrated that pristimerin suppressed NSCLC cells NCI-H1299 in vitro, exhibited potent activities of proliferation inhibition and apoptosis induction. Furthermore, the treatment of pristimerin decreased migration and invasion of H1299, which was correlated with EMT-related proteins and mRNA.

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Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Cited by 59 publications

References 31 publications

Costunolide induces apoptosis and inhibits migration and invasion in H1299 lung cancer cells

Costunolide induces apoptosis and inhibits migration and invasion in H1299 lung cancer cells

A novel oncotherapy strategy, direct thrombin inhibitors suppress progression, dissemination and spontaneous metastasis in non-small cell lung cancer

Pristimerin induces apoptosis and inhibits proliferation, migration in H1299 Lung Cancer Cells

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