Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

Shen, Xinyong; Zhi, Qiaoming; Wang, Yunliang; Li, Zhi; Zhou, Jin; Huang, Jian-An

doi:10.1159/000456066

Cited by 17 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that hypoxia induces resistance among various tumors. Previous reports showed that hypoxia can enhance drug resistance in non-small lung cancer cells [4]. Hypoxia-inducible factors are involved in chemotherapy resistance of breast cancer stem cells [5].…”

Section: Introductionmentioning

confidence: 98%

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

et al. 2020

View full text Add to dashboard Cite

Correspondence: Youguo Chen (youguo chen@163.com)Ovarian cancer (OC) is a malignant tumor with high mortality in women. Although cancer patients initially respond to paclitaxel chemotherapy following surgery, most patients will relapse after 12-24 months and gradually die from chemotherapy resistance. In OC, cancer cells become resistant to paclitaxel chemotherapy under hypoxic environment. The miR-27a has been identified as an oncogenic molecular in ovarian cancer, prostate cancer, liver cancer etc. In addition, the miR-27a is involved in hypoxia-induced chemoresistance in various cancers. However, the role of miR-27a in hypoxia-induced OC resistance remains unclear. The aim of the present study was to investigate the regulatory mechanism of miR-27a in hypoxia-induced OC resistance. The expression of HIF-1α induced Hypoxia overtly up-regulated. At the same time, hypoxia increased viability of Skov3 cells and decreased cell apoptosis when treated with paclitaxel. The expression of the miR-27a was obviously up-regulated under hypoxia and involved in hypoxia-induced paclitaxel resistance. Follow-up experiments portray that miR-27a improved paclitaxel resistance by restraining the expression of APAF1 in OC. Finally, we further elucidated the important regulatory role of the miR-27a-APAF1 axis in OC through in vivo experiments. According to our knowledge, we first reported the regulation of miR-27a in hypoxia-induced chemoresistance in OC, providing a possible target for chemoresistance treatment of OC.

show abstract

Section: Introductionmentioning

confidence: 98%

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Lung cancer, one of the most common cancer types in women and men, is currently the predominant cause of cancer-related deaths worldwide, resulting in more than one million deaths worldwide annually [ 1 ]. Non-small cell lung cancer (NSCLC) comprises almost 85% of all lung cancer cases [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of KLF5 suppresses hypoxia-induced resistance to cisplatin in NSCLC cells by regulating HIF-1α-dependent glycolysis through inactivation of the PI3K/Akt/mTOR pathway

et al. 2018

View full text Add to dashboard Cite

BackgroundHypoxia-mediated chemoresistance has been regarded as an important obstacle in the development of cancer treatment. Knockdown of krüppel-like factor 5 (KLF5) was reported to inhibit hypoxia-induced cell survival and promote cell apoptosis in non-small cell lung cancer (NSCLC) cells via direct regulation of hypoxia inducible factor-1α (HIF-1α) expression. However, the roles of KLF5 in the development of hypoxia-induced cisplatin (DDP) resistance and its underlying mechanism in NSCLC cells remain to be further elucidated.MethodsWestern blot was performed to determine the protein levels of KLF5, P-glycoprotein (P-gp) and HIF-1α in treated NSCLC cells. Cell survival was examined by MTT assay. The effect of KLF5 knockdown on hypoxia-induced glycolysis was assessed by measuring glucose consumption and lactate production. The effect of KLF5 knockdown on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway was analyzed by western blot.ResultsHypoxia upregulated the expression of KLF5 in NSCLC cells. KLF5 knockdown suppressed hypoxia-induced DDP resistance in NSCLC cells, as demonstrated by the increased cytotoxic effects of DDP and reduced P-gp expression in NSCLC cells in hypoxia. Moreover, KLF5 knockdown inhibited hypoxia-induced HIF-1α expression and glycolysis, and KLF5 knockdown suppressed hypoxia-induced DDP resistance by inhibiting HIF-1α-dependent glycolysis in NSCLC cells. Furthermore, KLF5 knockdown suppressed hypoxia-induced activation of the PI3K/Akt/mTOR pathway in NSCLC cells and KLF5 overexpression promoted hypoxia-induced DDP resistance in NSCLC cells through activation of the PI3K/Akt/mTOR pathway.ConclusionsKLF5 knockdown could suppress hypoxia-induced DDP resistance, and its mechanism may be due to the inhibition of HIF-1α-dependent glycolysis via inactivation of the PI3K/Akt/mTOR pathway.

show abstract

“…contributing to radio-or chemotherapeutic resistance (Klein et al, 2017;Shen et al, 2017). It thus serves as a prognostic marker of poor clinical outcome and the hypoxic microenvironment has become a focal area of cancer research and treatment.…”

mentioning

confidence: 99%

Blocking OLFM4/HIF‐1α axis alleviates hypoxia‐induced invasion, epithelial–mesenchymal transition, and chemotherapy resistance in non‐small‐cell lung cancer

Gao

Wang

Zhao

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia‐induced invasion, epithelial–mesenchymal transition (EMT), and chemotherapy resistance of non‐small‐cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia‐inducible factor (HIF)‐1α protein. The HIF‐1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia‐driven HIF‐1α production. Moreover, depletion of OLFM4 modulated multiple EMT‐associated proteins, as evidenced by the enhanced E‐cadherin levels along with the diminished expression of N‐cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF‐1α axis might be a potential therapeutic strategy for NSCLC.

show abstract

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

Cited by 17 publications

References 33 publications

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

Knockdown of KLF5 suppresses hypoxia-induced resistance to cisplatin in NSCLC cells by regulating HIF-1α-dependent glycolysis through inactivation of the PI3K/Akt/mTOR pathway

Blocking OLFM4/HIF‐1α axis alleviates hypoxia‐induced invasion, epithelial–mesenchymal transition, and chemotherapy resistance in non‐small‐cell lung cancer

Contact Info

Product

Resources

About