ArticleCancer biology & therapy2017
Simultaneous targeting of ATM and Mcl-1 increases cisplatin sensitivity of cisplatin-resistant non-small cell lung cancer.
Article in Cancer biology & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- FAM172A promotes epithelial ovarian cancer progression and induces platinum resistance via the PI3K/AKT pathway.Scientific reports · 2025Article
- The Role of miR-29a and miR-143 on the Anti-apoptotic MCL-1/cIAP-2 Genes Expression in EGFR Mutated Non-small Cell Lung Carcinoma Patients.Biochemical genetics · 2024Article
- Identification of Potent Inhibitors Targeting EGFR and HER3 for Effective Treatment of Chemoresistance in Non-Small Cell Lung Cancer.Molecules (Basel, Switzerland) · 2023Article
- Silence of URI in gastric cancer cells promotes cisplatin-induced DNA damage and apoptosis.American journal of cancer research · 2023Article
- Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance.Cancers · 2022Review
- Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells.World journal of surgical oncology · 2022Article
- A novel necroptosis-related LncRNA signature for prediction of prognosis and therapeutic responses of head and neck squamous cell carcinoma.Frontiers in pharmacology · 2022Article
- DNA repair pathways and their roles in drug resistance for lung adenocarcinoma.Molecular biology reports · 2021Review
- Chemosensitizing activity of peptide from Lentinus squarrosulus (Mont.) on cisplatin-induced apoptosis in human lung cancer cells.Scientific reports · 2021Article
- Mechanisms of resistance to chemotherapy in non-small cell lung cancer.Archives of pharmacal research · 2021Review
- Breathing New Life into the Mechanisms of Platinum Resistance in Lung Adenocarcinoma.Frontiers in cell and developmental biology · 2020Article
- Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis.Cancer management and research · 2020Article
- Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Article
- Whole-transcriptomic Profile of SK-MEL-3 Melanoma Cells Treated with the Histone Deacetylase Inhibitor: Trichostatin A.Cancer genomics & proteomicsArticle
Corrections and comments
- Erratum issuedCorrection.2020
- Erratum issuedCorrection.2021
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of cisplatin-resistance is an obstacle in non-small cell lung cancer (NSCLC) therapeutics. To investigate which molecules are associated with cisplatin-resistance, we analyzed expression profiles of several DNA repair and anti-apoptosis associated molecules in parental (A549P and H157P) and cisplatin-resistant (A549CisR and H157CisR) NSCLC cells. We detected constitutively upregulated nuclear ATM and cytosolic Mcl-1 molcules in cisplatin-resistant cells compared with parental cells. Increased levels of phosphorylated ATM (p-ATM) and its downstream molecules, CHK2, p-CHK2, p-53, and p-p53 were also detected in cisplatin-resistant cells, suggesting an activation of ATM signaling in these cells. Upon inhibition of ATM and Mcl-1 expression/activity using specific inhibitors of ATM and/or Mcl-1, we found significantly enhanced cisplatin-cytotoxicity and increased apoptosis of A549CisR cells after cisplatin treatment. Several A549CisR-derived cell lines, including ATM knocked down (A549CisR-siATM), Mcl-1 knocked down (A549CisR-shMcl1), ATM/Mcl-1 double knocked down (A549CisR-siATM/shMcl1) as well as scramble control (A549CisR-sc), were then developed. Higher cisplatin-cytotoxicity and increased apoptosis were observed in A549CisR-siATM, A549CisR-shMcl1, and A549CisR-siATM/shMcl1 cells compared with A549CisR-sc cells, and the most significant effect was shown in A549CisR-siATM/shMcl1 cells. In in vivo mice studies using subcutaneous xenograft mouse models developed with A549CisR-sc and A549CisR-siATM/shMcl1 cells, significant tumor regression in A549CisR-siATM/shMcl1 cells-derived xenografts was observed after cisplatin injection, but not in A549CisR-sc cells-derived xenografts. Finally, inhibitor studies revealed activation of Erk signaling pathway was most important in upregulation of ATM and Mcl-1 molcules in cisplatin-resistant cells. These studies suggest that simultaneous blocking of ATM/Mcl-1 molcules or downstream Erk signaling may recover the cisplatin-resistance of lung cancer.
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