Synergistic Induction of Erlotinib-Mediated Apoptosis by Resveratrol in Human Non-Small-Cell Lung Cancer Cells by Down-Regulating Survivin and Up-Regulating PUMA

Background/Aims: Lung cancer is one of the leading causes for cancer mortality. The poor therapeutic outcome of non-small cell lung carcinoma (NSCLC) is mainly due to late diagnosis and chemoresistance. In this study, we investigated the role of Musashi1 (MSI1) in NSCLC malignancy and chemoresistance. Methods: Colony formation, MTT, glucose uptake and lactate production assays were employed to study lung cancer cell malignancy and chemoresistance. RT-PCR and Western blotting were performed to detect mRNA and protein expressions of genes. We used immunohistochemistry and Pearson correlation analysis to study the relationship of gene expression. Results: We demonstrated that MSI1 was able to promote the proliferation and glucose metabolism of NSCLC cells, and to mediate the sensitivity to chemotherapy drugs in NSCLC cells. Importantly, we found that MSI1 could regulate the activity of Akt signaling. The regulation of NSCLC proliferation, glucose metabolism and chemoresistance by MSI1 was dependent on the modulation of the activity of the Akt signaling pathway. We also found that MSI1 was a target of miR-181a-5p, a microRNA involved in the regulation of cancer development. The expression levels of MSI1 and miR-181a-5p were negatively correlated in NSCLC. Conclusion: MSI1 promotes non-small cell lung carcinoma malignancy and chemoresistance via activating the Akt signaling pathway, which provides a new strategy for the therapy of NSCLC.

Section: Discussionmentioning

confidence: 99%

Musashi1 Promotes Non-Small Cell Lung Carcinoma Malignancy and Chemoresistance via Activating the Akt Signaling Pathway

Lang

Kong

et al. 2017

“…HLF, 95-D, A549, H1299, PC-9, H358 and H1650 cells were cultured in RPMI 1640 media (Gibco, Carlsbad, CA) supplemented with 10% fetal bovine serum (FBS) (Gibco, Carlsbad, CA) as previously described [20]. 293T cells were cultured in DMEM media (Gibco, Carlsbad, CA) supplemented with 10% FBS.…”

Section: Cell Culturementioning

confidence: 99%

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer

Zhang

Qiao

et al. 2016

Background/Aims: Deregulation of microRNAs (miRNAs) expression is a frequent event in cancer development and progression. Recent studies have implied that abnormal expression of miRNAs is frequently observed in non-small cell lung cancer (NSCLC). Here, we examined the levels and biological functions of miR-509-5p in NSCLC. Methods: The levels of miR-509-5p were measured by real-time quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with adjacent normal tissues. Cell viability was analyzed by MTT and colony formation assay. Cell migration and invasion were evaluated by transwell and wound healing assay. In addition, we predicted the putative targets of miR-509-5p by bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the relationship between miR-509-5p and the target in NSCLC cells. Results: miR-509-5p expression was significantly reduced in NSCLC tissues compared with adjacent normal tissues. In addition, miR-509-5p decreased cell proliferation, migration and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase reporter assay showed miR-509-5p could bind to the 3' untranslational regions of FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability, migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299 cells. Conclusions: miR-509-5p exerts tumor-suppressive effects by attenuating FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR-509-5p may be considered as a novel and potential target for the diagnosis, prognosis and treatment of NSCLC.

“…The prognosis of LC is still unsatisfying, and 5-year survival rate is just 11% [4]. Current LC treatment approaches are mainly limited to radiotherapy, chemotherapy, surgical resection, immunomodulatory therapy and targeted therapy for tumor removal [5-8]. At present, platinum-based chemotherapy represents the primary treatment approach for advanced cases of LC.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.