Abstract:
Background:Several EGFR-tyrosine kinase inhibitors (TKIs), such as gefitinib (Gef), have been used as effective clinical therapies for patients with non-small cell lung cancer (NSCLC). However, due to acquired resistance, the efficacy of Gef treatment is severely blocked. Our preliminary study found that epigallocatechin gallate (EGCG) in combination with Gef could work synergistically to increase the sensitivity to Gef in NSCLC, but the mechanisms responsible for this have not been completely defined. Purpose:In our present study, we devoted to investigate the synergistic effects of combined EGCG and Gef treatment and the importance of autophagy and ERK signaling pathway in overcoming acquired drug resistance to Gef in NSCLC. Methods:We evaluated the synergistic effects of combined EGCG and Gef treatment through in vitro cell proliferation/viability assays and in vivo xenograft studies, respectively. Autophagic flux was assessed by GFP-microtubule-associated protein 1 light chain 3 (LC3) plasmid transfection and western blot detection of autophagy-related proteins. Besides, the role of ERK on acquired resistance was validated with a ERK inhibitor. Results:We discovered that EGCG can synergize with Gef to inhibit the proliferation of Gef-resistant NSCLC cells and suppress tumor growth in a xenograft mouse model. The underlying mechanisms of synergism were investigated, and the results showed that co-treatment with Gef and EGCG could inhibit Gef-induced autophagy and ERK phosphorylation. Consistently, the expression of LC3-II/I and ATG5 were inhibited, whereas the expression of p62 was enhanced in EGCG and Gef combination treatment groups. Further, inhibition of autophagy in Gef-resistant A549 cells could augment cell death. Conclusion:In conclusion, EGCG overcomes Gef resistance by inhibiting autophagy and augmenting cell death through targeting ERK pathway in NSCLC. Gef and EGCG combination therapy may be an effective strategy to overcome acquired resistance in NSCLC.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Meng J,Chang C,Chen Y,Bi F,Ji C,Liu Wdoi
10.2147/OTT.S209441subject
Has Abstractpub_date
2019-07-26 00:00:00pages
6033-6043issn
1178-6930pii
209441journal_volume
12pub_type
杂志文章abstract:Background:Our previous study demonstrated that Id-1 may promote the tumorigenicity of esophageal squamous cell carcinoma (ESCC). Id-4 is another member of Id family, which is rare to be studied in ESCC. In this study, we investigated the expression of Id-4 in human ESCC specimens and determined whether Id-4 expression...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S230678
更新日期:2020-02-12 00:00:00
abstract::Erastin was initially discovered as a small molecule compound that selectively kills tumor cells expressing ST and RASV12 and was later widely investigated as an inducer of ferroptosis. Ferroptosis is a recently discovered form of cell death caused by peroxidation induced by the accumulation of intracellular lipid rea...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S254995
更新日期:2020-06-11 00:00:00
abstract:BACKGROUND:The prognostic and predictive significance of the high-level microsatellite instability (MSI-H) phenotype in various malignancies is unclear. We describe the characteristics, clinical course, and outcomes of patients with MSI-H malignancies treated in a real-life hospital setting. PATIENTS AND METHODS:A ret...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S126905
更新日期:2017-03-29 00:00:00
abstract:BACKGROUNDS:Sitting time and physical activity are associated with cancer risk; however, their roles in the development of esophageal squamous cell carcinoma (ESCC) are inconclusive. This study aimed to investigate the effects of total sitting time, occupational activity time (OAT), and recreational activity time (RAT)...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S147711
更新日期:2017-09-27 00:00:00
abstract:Purpose:Cervical squamous cell carcinoma (CSCC) seriously affects women's health worldwide, and it is of great significance to illuminate the specific role of circRNAs in CSCC. Materials and Methods:Three mRNA datasets, two miRNA datasets and one circRNA dataset of CSCC, downloaded from GEO, were utilized in this stud...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S254323
更新日期:2020-08-25 00:00:00
abstract:Background:Emerging researches have demonstrated that aberrantly expressed long non-coding RNAs (lncRNAs) have great significance in non-small cell lung cancer (NSCLC) progression. The aim of this study was to explore the role of lncRNA AZIN1 antisense RNA 1 (AZIN1-AS1) in NSCLC and the related mechanism. Methods:Expr...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S261497
更新日期:2020-10-09 00:00:00
abstract::Androgen deprivation therapy (ADT) is well established as a backbone therapy for metastatic prostate cancer (mPCa), and both European and American guidelines emphasize the importance of maintaining ADT after progression to metastatic castration-resistant prostate cancer (CRPC). However, the use of ADT varies widely in...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S117176
更新日期:2016-11-29 00:00:00
abstract::[This corrects the article DOI: 10.2147/OTT.S227758.]. ...
journal_title:OncoTargets and therapy
pub_type: 已发布勘误
doi:10.2147/OTT.S242712
更新日期:2020-01-29 00:00:00
abstract:OBJECTIVE:To investigate the effects of microRNA-122 (miR-122) on proliferation, migration, and invasion in human hepatocellular carcinoma (HCC) cells by activating epithelial-mesenchymal transition (EMT) pathways. METHODS:miR-122 mimics, miR-122 inhibitors, relevant control oligonucleotides, and Wnt1 were transfected...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S92378
更新日期:2016-04-06 00:00:00
abstract:Background:Leukemia related protein 16 (LRP16), one of the genes belonging to the macro domain family, has been found up-regulated in various tumors including testicles, ovaries and mucosa of colon and is associated with poor clinical outcomes. Purpose:The objective of this study was to investigate expression pattern ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S157914
更新日期:2018-03-05 00:00:00
abstract:Background:Many studies have explored the prognostic value of T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) and its association with lymphatic metastasis in malignant solid tumors, but the conclusions remain controversial. Therefore, we performed a meta-analysis to systematically assess the prognost...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S191571
更新日期:2019-07-25 00:00:00
abstract:Objective:To compare cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and CHOP plus etoposide (CHOPE) with regard to outcomes including efficacy and safety for patients with peripheral T-cell lymphoma (PTCL). Methods:Relevant literature was searched using PubMed, Embase, Wanfang, and CNKI for eligible...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S189825
更新日期:2019-03-28 00:00:00
abstract::Liver cancer is a common malignant disease in China, while the primary hepatic neuroendocrine tumor (PHNET) is extremely rare presented with various manifestations. We herein describe an interesting PHNET case, which was clinically diagnosed as hepatocellular carcinoma (HCC) based on strong clinical evidence and the n...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S236728
更新日期:2020-02-03 00:00:00
abstract::ALK rearrangements account for ~5% of non-small-cell lung cancer (NSCLC). Numerous rearrangement partners have been discovered. Here, we describe a 53-year-old nonsmoker with NSCLC, in whom we identified four novel rearrangements. The patient was diagnosed as adenocarcinoma in the right middle lobe of lung, with metas...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S258067
更新日期:2020-08-20 00:00:00
abstract:Background:miR520a-3p has previously had its antitumorigenic role in various types of cancers revealed, and been predicted as a posttranscriptional regulator of the NFκB-subunit RELA gene. Thus, miR520a-3p could function in carcinogenesis through suppressing RELA. Methods:Expression of miR520a-3p and RELA mRNA was qua...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S208889
更新日期:2019-08-14 00:00:00
abstract:AIMS:Metastasis-associated gene 2 (MTA2) is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC). The aim of the study was to explore the expression and function of MTA2 in NPC. METHODS:Expression of MTA2 in NPC tissues and cell lines was...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S96518
更新日期:2016-03-18 00:00:00
abstract:Objective:Long non-coding RNA (lncRNA) ANRIL is emerging as a crucial role in ovarian cancer progression and prognosis. However, the precise molecular mechanism of ANRIL on ovarian cancer is not known. Thus, we aim to study the underlying mechanism of ANRIL on the action. Methods:The MTT assay assessed cell viability....
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S273614
更新日期:2021-01-19 00:00:00
abstract:Background and objective:Endometrial carcinoma (EC) is one of the most frequently diagnosed malignancies in females. Dysregulation of lncRNA TDRG1 has been widely documented in several cancers, including EC. However, the mechanism of this lncRNA involving in EC progression remains to be further elucidated. Materials a...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S228168
更新日期:2019-12-11 00:00:00
abstract:BACKGROUND:Activating transcription factor 5 (ATF5) is a member of the activating transcription/cAMP response element-binding protein family of basic leucine zipper proteins that plays an important role in cell survival, differentiation, proliferation, and apoptosis. The ATF5 gene generates two transcripts: ATF5 isofor...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S113194
更新日期:2016-10-11 00:00:00
abstract:PURPOSE:Programmed death-ligand 1 (PD-L1) is found to be overexpressed in non-small cell lung cancer. The present study intended to evaluate the status of PD-L1 expression in patients with resection and recurrent lung adenocarcinoma. PATIENTS AND METHODS:Matched resection and recurrent tumor samples were harvested fro...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S127498
更新日期:2017-04-06 00:00:00
abstract:BACKGROUND:Lapatinib is a dual epidermal growth factor receptor (EGFR) and HER2 inhibitor. Overexpression of these receptors is frequently observed in head and neck squamous cell carcinoma (HNSCC). As growing proportion of HNSCC is characterized by human papillomavirus (HPV) infection, we aimed at evaluating the effica...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S68235
更新日期:2015-02-02 00:00:00
abstract::Lung cancer is the leading cause of cancer-related mortality in both sexes, accounting for over one quarter of cancer deaths. Non-small-cell lung cancer (NSCLC) comprises 85%-90% of lung cancer diagnoses and despite advances in multimodality therapies, 5-year survival rates remain dismal with a median survival for pat...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S67262
更新日期:2015-04-20 00:00:00
abstract:Background:Cellular senescence-inhibited gene (CSIG) strongly prolongs the progression of replicative senescence. However, roles and mechanisms of CSIG in tumor progression have not been studied widely. Methods:Roles of CSIG in migration and proliferation of SMMC7721 and Huh7 cells were analyzed by transwell or cell v...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S188449
更新日期:2019-03-15 00:00:00
abstract:Purpose:Hepatocellular carcinoma (HCC) has a high incidence in China and exploring effective ways for early diagnosis is an important method to improve the prognosis of patients with HCC. Additional studies reported that. Some kinds of microRNA (miRNA) in plasma will change accordingly during HCC progress, and this cha...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S232453
更新日期:2020-03-09 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate the therapeutic efficacy and safety of trastuzumab emtansine (T-DM1) for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer. METHODS:We performed a systemic review and meta-analysis of the relevant published clinical studies. A c...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S100499
更新日期:2016-02-29 00:00:00
abstract:Purpose:Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 s...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S196914
更新日期:2019-03-27 00:00:00
abstract:Introduction:The purpose of present study was to investigate the effect of limonin on tumor glycolysis and the underlying mechanisms in hepatocellular carcinoma (HCC). Methods:Cell proliferation and colony formation assays were performed to evaluate the potency of limonin against HCC cells in vitro. The glucose consum...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S165220
更新日期:2018-07-03 00:00:00
abstract::Programmed cell death-1 (PD-1) immune checkpoint inhibitors have exhibited promising efficacy in various types of tumors. Here, we report an unresectable locally advanced gastric cancer (GC) with programmed cell death ligand-1 (PD-L1) positive and microsatellite instability (MSI), which exhibiting an unexpected effica...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S243298
更新日期:2020-02-26 00:00:00
abstract:BACKGROUND:CD155, an immunoglobulin-like adhesion molecule, plays an important role in carcinoma such as cells migration, proliferation, metastasis, and tumor immune. The upregulation of CD155 has been found in several human malignancies, but its expression in cholangiocarcinoma (CCA) still remains unclear. The aim of ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S141476
更新日期:2017-07-31 00:00:00
abstract:Purpose:Radioresistance is a vital obstacle for the prognosis of human nasopharyngeal carcinoma (NPC), but the underlying mechanism is still unknown. Here, we explored the role of the NRF2/KEAP1 pathway in radioresistance of NPC cell lines. Materials and Methods:We selected NPC cell lines CNE-1 and CNE-2, treated them...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S260169
更新日期:2020-09-11 00:00:00