Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer

Cui, Fei; Wang, Wei; Wu, Duoguang; He, Xiaotian; Wu, Jing; Wang, M.

doi:10.1007/s12094-015-1424-6

Cited by 12 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zheng et al revealed that CTSL inhibition enhances the availability of cytoplasmic and nuclear protein drug targets, including estrogen receptor-α, Bcr-Abl, topoisomerase-IIα, histone deacetylase 1, and androgen receptor [9] . CTSL suppression also improves gefitinib resistance in non-small cell lung cancer [14] , and CTSL knockdown can increase the sensitivity of ovarian cancer cells to paclitaxel [38] . Our previous study also suggested that CTSL may be a novel therapeutic target to prevent tumor cells from becoming resistant to chemotherapy and to reinforce the efficiency of paclitaxel and cisplatin against lung cancer [12] .…”

Section: Discussionmentioning

confidence: 99%

“…Then we indicated that CTSL also regulates drug resistance by mediating EMT through its effects on the expression of EMT-associated transcription factors, Snail, Slug, ZEB1, and ZEB2 [12] . The overexpression of CTSL is associated with the chemoresistance and invasion of epithelial ovarian cancer [13] and is related to gefitinib resistance in lung cancer [14] . Increased CTSL levels are associated with the increased chemoresistance of tumor cells and may be applied to gene therapy [15] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial–mesenchymal transition

et al. 2017

View full text Add to dashboard Cite

Cathepsin L (CTSL), a cysteine protease, is closely related to tumor occurrence, development, and metastasis, and possibly regulates cancer cell resistance to chemotherapy. miRNAs, especially the miR-200 family, have been implicated in drug-resistant tumors. In this study we explored the relationship of CTSL, miRNA-200c and drug resistance, and the potential regulatory mechanisms in human lung cancer A549 cells and A549/TAX cells in vitro. A549/TAX cells were paclitaxel-resistant A549 cells overexpressing CTSL and characterized by epithelial-mesenchymal transition (EMT). We showed that miRNA-200c and CTSL were reciprocally linked in a feedback loop in these cancer cells. Overexpression of miRNA-200c in A549/TAX cells decreased the expression of CTSL, and enhanced their sensitivity to paclitaxel and suppressed EMT, whereas knockdown of miRNA-200c in A549 cells significantly increased the expression of CTSL, and decreased their sensitivity to paclitaxel and induced EMT. Overexpression of CTSL in A549 cells significantly decreased the expression of miRNA-200c, and reduced their sensitivity to paclitaxel and induced EMT, but these effects were reversed by miRNA-200c, whereas knockdown of CTSL in A549/TAX cells attenuated paclitaxel resistance and remarkably inhibited EMT, but the inhibition of miRNA-200c could reverse these effects. Therefore, miRNA-200c may be involved in regulating paclitaxel resistance through CTSL-mediated EMT in A549 cells, and CTSL and miRNA-200c are reciprocally linked in a feedback loop.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial–mesenchymal transition

et al. 2017

View full text Add to dashboard Cite

show abstract

“…CTSL inhibition in drug-resistant cells not only facilitates the induction of senescence, it also prevents drug resistance [6, 7]. The upregulation of CTSL in human cancers contributes to tumor growth and survival, and to resistance of PC9 cells to the chemotherapeutic drug gefitinib [8]. Additionally, silencing CTSL can prevent the drug resistance of tumor cells, reduce the proliferation of ovarian cancer cells, weaken the cell invasion and migration properties, and increase the sensitivity of cells to paclitaxel [9–11].…”

Section: Introductionmentioning

confidence: 99%

Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms

Zhao

Zhu

Wang

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Cathepsin L (CTSL) is a cysteine protease known to have important roles in regulating cancer cellular resistance to chemotherapy. However mechanism underlying which regulates CTSL-mediated drug resistance remain largely unknown. Methods We used NSCLC cell lines: A549, A549/TAX (paclitaxel-resistant), A549/DDP (cisplatin-resistant), H460 and PC9 cells, to evaluate CTSL and drug resistance changes. Tumor specimens from 53 patients with NSCLC and Xenograft models was also utilized to explore the regulatory relationship of CTSL, TGF-β, Egr-1 and CREB. Results TGF-β and smad3 were overexpressed only in A549/TAX cells, silencing TGF-β or smad3 in A549/TAX cells decreased the expression of CTSL and enhanced their sensitivity to paclitaxel. Smad3 binds to the Smad-binding-element(SBE) of the CTSL promoter, resulting in increased activity of the CTSL promoter and subsequent CTSL. Egr-1 and CREB were overexpressed only in A549/DDP cells, and silencing Egr-1 or CREB reduced the expression of CTSL and increased cisplatin cytotoxicity. CREB could affect the activity of the CTSL promoter by binding to it. And the potential regulatory factors of CTSL were consistent in vivo and in human lung cancer. These different regulatory mechanisms of CTSL-mediated drug resistance exist in two other NSCLC cell lines. Conclusion CTSL-mediated drug resistance to paclitaxel and cisplatin may be modulated by different mechanisms. The results of our study identified different mechanisms regulating CTSL-mediated drug resistance and identified smad3 as a novel regulator of CTSL. Electronic supplementary material The online version of this article (10.1186/s13046-019-1299-4) contains supplementary material, which is available to authorized users.

show abstract

“…A previous study examined the effect of NKG2-D-activating natural killer cell receptor expression in NSCLC cells, and revealed that gefitinib attenuated NK cell-mediated cell death (27). However, the use of gefitinib may induce gefitinib-resistant NSCLC via the overexpression of cathepsin L (28). Therefore, the combination of gefitinib with other drugs may increase the killing of NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

Yellow and green pigments from Calophyllumï¿½inophyllum L. seed oil induce cell death in colon and lung cancer cells

et al. 2018

View full text Add to dashboard Cite

Abstract. Natural compounds have been candidates for anticancer medicine over the last 20 years. During the process of isolating seed oil from Calophyllum inophyllum L., yellow and green pigments containing multiple compounds with an aromatic structure were identified. High-performance liquid chromatography and nuclear magnetic resonance analysis of these pigments revealed that the compounds present were identical, but the concentration of the compounds was different. Treatment with the pigments was able to induce the death of DLD-1 human colon cancer cells and increase the percentage of the cells in the sub-G 1 and sub-G 2 /M phases in a dose-dependent manner. Additionally, the pigments were able to exhibit cytotoxic activity on A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines at 24 h, with half-maximal inhibitory concentrations (IC 50 ) values of 0.1206 and 0.0676%, respectively for green pigments, and 0.0434 and 0.0501%, respectively for yellow pigments. Furthermore, a decrease in IC 50 value was associated with an increase in the duration of treatment. However, a sharp decrease in IC 50 value of the yellow pigment was observed for H1975 cells at 48 h and for A549 cells at 72 h compared with no change in IC 50 value for the green pigment with time, suggesting that the pigments function and induce cell death differently in the two cell lines. An investigation was performed into the synergistic effect of the green pigment and gefitinib (Iressa ® , ZD1839), which is a selective epidermal growth factor receptor-tyrosine kinase inhibitor to block growth factor-mediated cell proliferation. The combination of the green pigment and gefitinib resulted in an enhancement of the decrease in viability of A549 and H1975 cells compared with treatment with gefitinib alone, which suggested that treatment with the green pigments was able to enhance the sensitivity of NSCLC cells to gefitinib. In conclusion, these pigments may be considered for development as anti-colon cancer agents.

show abstract

Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer

Cited by 12 publications

References 15 publications

A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial–mesenchymal transition

A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial–mesenchymal transition

Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms

Yellow and green pigments from Calophyllumï¿½inophyllum L. seed oil induce cell death in colon and lung cancer cells

Contact Info

Product

Resources

About