scholarly journals Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization

2017 ◽  
Vol 42 (5) ◽  
pp. 1789-1801 ◽  
Author(s):  
Jia Shen ◽  
Hailin Ma ◽  
Tiancheng Zhang ◽  
Hui Liu ◽  
Linghua Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Colony Formation ◽  
Xenograft Model ◽  
Small Cell ◽  
Cell Cycle Regulators ◽  
Small Cell Lung ◽  
Microtubule Polymerization

Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC) cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.

scholarly journals Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2136-2147 ◽  
Author(s):  
Haiting Gu ◽  
Junfeng Chen ◽  
Yukang Song ◽  
Haiyan Shao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Non Coding Rna

Background/Aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC). Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. The effect of GAPLINC on cell proliferation was investigated using CCK8-assay, colony formation assay, and xenograft model. The effects of GAPLINC on apoptosis and cell cycle were determined using flow cytometry. The mechanism of GAPLINC involved in NSCLC was explored using Western blot, luciferase reporter assay, and RNA fluorescence in situ hybridization. Results: We found that GAPLINC expression was up-regulated in NSCLC tissues and cell lines. Overexpression of GAPLINC was associated with poor prognosis in patients with NSCLC. Silencing of GAPLINC significantly inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G0/G1 phase. Results from xenograft transplantation showed that GAPLINC silencing inhibited the tumor growth in vivo. Interestingly, GAPLINC silencing decreased the expression of eukaryotic elongation factor-2 kinase (eEF2K) protein both in vivo and in vitro. Bioinformatic analysis and luciferase reporter confirmed that miR-661 targeted GAPLINC and eEF2K 3’-UTR and was negatively correlated with the expression of GAPLINC and eEF2K. Conclusion: Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy.

scholarly journals Circ_ZFR contributes to the paclitaxel resistance and progression of non-small cell lung cancer by upregulating KPNA4 through sponging miR-195-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junmin Li ◽  
Rongmei Fan ◽  
Hui Xiao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Xenograft Model ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background A growing body of evidence has demonstrated the vital roles of circular RNAs (circRNAs) in cancer progression and drug resistance. We intended to explore the roles and mechanisms of circ_ZFR in the paclitaxel (PTX) resistance and progression of non-small cell lung cancer (NSCLC). Methods Two NSCLC cell lines A549 and H460 were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to measure the levels of circ_ZFR, ZFR, miR-195-5p and karyopherin subunit alpha 4 (KPNA4) mRNA. RNase R assay was used to analyze the characteristic of circ_ZFR. MTT assay was carried out to assess PTX resistance and cell proliferation. Flow cytometry analysis was utilized to analyze cell cycle and apoptosis. Transwell assay was used to examine cell migration and invasion. Western blot assay was conducted to measure the protein levels of Ki67, Twist1, E-cadherin and KPNA4. Dual-luciferase reporter assay was adopted to verify the combination between miR-195-5p and circ_ZFR or KPNA4. Murine xenograft model assay was used to investigate the effect of circ_ZFR on PTX resistance of NSCLC in vivo. Results Circ_ZFR level was enhanced in PTX-resistant NSCLC tissues and cells. Knockdown of circ_ZFR suppressed PTX resistance, cell cycle process, proliferation, migration and invasion and induced apoptosis in PTX-resistant NSCLC cells. For mechanism analysis, circ_ZFR knockdown markedly downregulated the expression of KPNA4 by sponging miR-195-5p, thereby promoting PTX sensitivity and suppressing cell progression in PTX-resistant NSCLC cells. In addition, circ_ZFR silencing enhanced PTX sensitivity of NSCLC in vivo. Conclusion Circ_ZFR knockdown played a positive role in overcoming PTX resistance of NSCLC via regulating miR-195-5p/KPNA4 axis, which might provide a possible circRNA-targeted therapy for NSCLC.

CALCR knockdown inhibits the development and progression of non-small-cell lung cancer

2021 ◽  
Author(s):  
Tao He ◽  
Feng Ling
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Expression Level ◽  
Cell Counting ◽  
Small Cell Lung

Abstract G protein-coupled receptors (GPCRs) have been reported to participant in the occurrence and development of a variety of human cancers. CALCR is one of the hundreds of GPCRs, but its expression level and functional importance have never been investigated in non-small-cell lung cancer (NSCLC). In the present study, the protein expression level of CALCR was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound healing assay and the transwell assay were performed to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed to conduct the in vivo experiments. The results indicated that the CALCR expression was abundantly up-regulated in NSCLC and positively related to tumor infiltrate. Besides, CALCR knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study verified the inhibitory effects of CALCR knockdown on NSCLC tumorigenesis. The abovementioned results provided a reference for the treatment of NSCLC, that was, CALCR knockdown might be a considerable therapeutic strategy.

scholarly journals Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

2018 ◽  
Vol 45 (5) ◽  
pp. 1807-1817 ◽  
Author(s):  
Jia Shen ◽  
Banghua Wang ◽  
Tao Zhang ◽  
Ni Zhu ◽  
Zexia Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Invasion ◽  
Small Cell ◽  
Small Cell Lung

Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development

Oncogene ◽  
2018 ◽  
Vol 38 (14) ◽  
pp. 2580-2594 ◽  
Author(s):  
Yo-Taro Shirai ◽  
Anna Mizutani ◽  
Saori Nishijima ◽  
Masafumi Horie ◽  
Chisato Kikuguchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cancer Development ◽  
Cell Cycle Regulators ◽  
Small Cell Lung ◽  
Negative Cell

scholarly journals Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

2018 ◽  
Vol 51 (5) ◽  
pp. 2324-2340 ◽  
Author(s):  
Xiuyuan Li ◽  
Zenglei Zhang ◽  
Hua Jiang ◽  
Qiang Li ◽  
Ruliang Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Promoter Region ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

scholarly journals Hedyotis diffusa plus Scutellaria barbata Suppress the Growth of Non-Small-Cell Lung Cancer via NLRP3/NF-Κb/MAPK Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ya-Xin Lv ◽  
Hao-Ran Pan ◽  
Xin-Ying Song ◽  
Qing-Qi Chang ◽  
Dan-Dan Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Mapk Signaling ◽  
Small Cell ◽  
Small Cell Lung ◽  
Scutellaria Barbata ◽  
Hedyotis Diffusa ◽  
Mapk Signaling Pathways

Hedyotis diffusa (HD) plus Scutellaria barbata (SB) have been widely used in antitumor clinical prescribes as one of herb pairs in China. We investigated the effect of aqueous extract from Hedyotis diffusa plus Scutellaria barbata at the equal weight ratio (HDSB11) in inhibiting the growth of murine non-small-cell lung cancer cell (NSCLC) line LLC in vivo and in vitro in this study. Compared with other aqueous extracts, HDSB11 showed the lowest IC50 in inhibiting cell proliferation at 0.43 mg/ml. Besides, HDSB11 effectively suppressed colony formation and induced cell apoptosis. The further assessment of HDSB11 on the murine Lewis-lung-carcinoma-bearing mouse model showed it significantly inhibited tumors’ bioluminescence at the dose of 30 g crude drug/kg. Mechanistically, HDSB11 attenuated the expressions of NLRP3, procaspase-1, caspase-1, PRAP, Bcl-2, and cyclin D1 and downregulated the phosphorylation levels of NF-κB, ERK, JNK, and p38 MAPK. In conclusion, HDSB11 could alleviate cell proliferation and colony formation and induce apoptosis in vitro and tumor growth in vivo, partly via NF-κB and MAPK signaling pathways to suppress NLRP3 expression.

scholarly journals Effect of Lncrna FER1L4 Overexpression on Prognosis and Cell Proliferation in Non-Small Cell Lung Cancer

2021 ◽  
Author(s):  
Xiang Jin ◽  
Xingang Liu ◽  
Huiqin Zhu ◽  
Yinghui Guan
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Size ◽  
Colony Formation ◽  
Small Cell ◽  
Normal Lung ◽  
Colony Formation Assay ◽  
Small Cell Lung ◽  
Over Expression ◽  
Favorable Prognosis

Abstract Background: The purpose of this study was to investigate the clinical significance and biological function of lncRNA FER1L4 in NSCLC. Methods: A total of 114 cases of NSCLC tissues and matched normal lung tissues were obtained from The first hospital of Jilin University between January 2009 and December 2016. The clinicopathological characteristics of patients were collected, including age, gender, tumor size, etc. The expression levels of LncRNA FER1L4 were detected by qRT-PCR. Non-small cell lung cancer cell lines (A549, H292 and H1299) were cultured with LncRNA FER1L4 mimics and LncRNA FER1L4 inhibitor. Cell proliferation was evaluated by CCK-8 and colony formation assay. Results: The expression levels of lncRNA FER1L4 were significantly lower in NSCLC tissues compared with those in matched normal lung tissues (P<0.05). Decreased level of lncRNA FER1L4 was significantly correlated with tumor size, TNM stage and lymph node metastasis (P<0.05). Moreover, lncRNA FER1L4 over-expression predicted favorable prognosis in NSCLC (P<0.05). Furthermore, CCK-8 and colony formation assay showed that lncRNA FER1L4 over-expression significantly suppressed cell proliferation. Conclusions: Our results suggested that LncRNA FER1L4 overexpression predicted favorable prognosis and suppressed cell proliferation in NSCLC, which may serve as a promising therapeutic target.

20(S)-Ginsenoside Rg3 Inhibits Lung Cancer Cell Proliferation by Targeting EGFR-Mediated Ras/Raf/MEK/ERK Pathway

2021 ◽  
pp. 1-13
Author(s):  
Yuan Liang ◽  
Tiehua Zhang ◽  
Siyuan Jing ◽  
Peng Zuo ◽  
Tiezhu Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
G1 Phase ◽  
Erk Pathway ◽  
Ginsenoside Rg3 ◽  
Small Cell Lung ◽  
Triterpenoid Saponins

Lung cancer is the leading cause of cancer death in the world and classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). As tyrosine kinase inhibitors (TKIs), several triterpenoid saponins can target to epidermal growth factor receptor (EGFR), a widely used molecular therapeutic target, to exhibit remarkable anti-proliferative activities in cancer cells. As one of triterpenoid saponins, 20([Formula: see text])-ginsenoside Rg3 [20([Formula: see text])-Rg3] was confirmed to be an EGFR-TKI in this work. According to the quantitative real-time reverse transcription-PCR (qRT-PCR) and immunoblotting analysis, 20([Formula: see text])-Rg3 was certified to play a key role on EGFR/Ras/Raf/MEK/ERK signal pathway regulation. Our data demonstrated that 20([Formula: see text])-Rg3 might block the cell cycle at the G0/G1 phase by downregulating CDK2, Cyclin A2, and Cyclin E1. Molecular docking suggested that the combination of both hydrophobic and hydrogen-bonding interactions may help stabilizing the 20([Formula: see text])-Rg3-EGFR binding. Furthermore, their binding stability was assessed by molecular dynamics simulation. Taken together, these data provide the evidence that 20([Formula: see text])-Rg3 could prohibit A549 cell proliferation, probably by arresting the cell cycle at the G0/G1 phase via the EGFR/Ras/Raf/MEK/ERK pathway.

Sign in / Sign up

Export Citation Format

Share Document